Tanaka K

References (55)

Title : Hybrid pharmacophore design and synthesis of donepezil-inspired aurone derivative salts as multifunctional acetylcholinesterase inhibitors - Funahashi_2024_Bioorg.Chem_145_107229
Author(s) : Funahashi R , Matsuura F , Ninomiya M , Okabe S , Takashima S , Tanaka K , Nishina A , Koketsu M
Ref : Bioorg Chem , 145 :107229 , 2024
Abstract : Flavonoids, a ubiquitous group of plant polyphenols, are well-known for their beneficial effects on human health. Their phenylchromane skeletons have structural similarities to donepezil [the US FDA-approved drug used to treat Alzheimer's disease (AD)]. The objective of this study was to design and synthesize valuable agents derived from flavonoids for relieving the symptoms of AD. A variety of flavonoid derivative salts incorporating benzylpyridinium units were synthesized and several of them remarkedly inhibited acetylcholinesterase (AChE) activity in vitro. Additionally, aurone derivative salts protected against cell death resulting from t-BHP exposure in rat pheochromocytoma PC12 cells and slightly promoted neurite outgrowth. Furthermore, they potently suppressed the aggregation of amyloid-beta (Abeta(1-42)). Our findings highlight the effectiveness of donepezil-inspired aurone derivative salts as multipotent candidates for AD.
ESTHER : Funahashi_2024_Bioorg.Chem_145_107229
PubMedSearch : Funahashi_2024_Bioorg.Chem_145_107229
PubMedID: 38401360

Title : Activation of Strigolactone Biosynthesis by the DWARF14-LIKE\/KARRIKIN-INSENSITIVE2 Pathway in Mycorrhizal Angiosperms, but Not in Arabidopsis, a Non-mycorrhizal Plant - Mashiguchi_2023_Plant.Cell.Physiol_64_1066
Author(s) : Mashiguchi K , Morita R , Tanaka K , Kodama K , Kameoka H , Kyozuka J , Seto Y , Yamaguchi S
Ref : Plant Cell Physiol , 64 :1066 , 2023
Abstract : Strigolactones (SLs) are a class of plant hormones that regulate many aspects of plant growth and development. SLs also improve symbiosis with arbuscular mycorrhizal fungi (AMF) in the rhizosphere. Recent studies have shown that the DWARF14-LIKE (D14L)/KARRIKIN-INSENSITIVE2 (KAI2) family, paralogs of the SL receptor D14, are required for AMF colonization in several flowering plants, including rice. In this study, we found that (-)-GR5, a 2'S-configured enantiomer of a synthetic SL analog (+)-GR5, significantly activated SL biosynthesis in rice roots via D14L. This result is consistent with a recent report, showing that the D14L pathway positively regulates SL biosynthesis in rice. In fact, the SL levels tended to be lower in the roots of the d14l mutant under both inorganic nutrient-deficient and -sufficient conditions. We also show that the increase in SL levels by (-)-GR5 was observed in other mycorrhizal plant species. In contrast, the KAI2 pathway did not upregulate the SL level and the expression of SL biosynthetic genes in Arabidopsis, a non-mycorrhizal plant. We also examined whether the KAI2 pathway enhances SL biosynthesis in the liverwort Marchantia paleacea, where SL functions as a rhizosphere signaling molecule for AMF. However, the SL level and SL biosynthetic genes were not positively regulated by the KAI2 pathway. These results imply that the activation of SL biosynthesis by the D14L/KAI2 pathway has been evolutionarily acquired after the divergence of bryophytes to efficiently promote symbiosis with AMF, although we cannot exclude the possibility that liverworts have specifically lost this regulatory system.
ESTHER : Mashiguchi_2023_Plant.Cell.Physiol_64_1066
PubMedSearch : Mashiguchi_2023_Plant.Cell.Physiol_64_1066
PubMedID: 37494415

Title : Anti-GPIHBP1 Antibody-Positive Autoimmune Hyperchylomicronemia and Immune Thrombocytopenia - Tanaka_2022_J.Atheroscler.Thromb__
Author(s) : Tanaka K , Koseki M , Kato H , Miyashita K , Okada T , Kanno K , Saga A , Chang J , Omatsu T , Inui H , Ohama T , Nishida M , Yamashita S , Sakata Y
Ref : J Atheroscler Thromb , : , 2022
Abstract : Primary hyperchylomicronemia is characterized by marked hypertriglyceridemia exceeding 1,000 mg/dL. It is caused by dysfunctional mutations in specific genes, namely those for lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), apolipoprotein C2 (ApoC-II), lipase maturation factor 1 (LMF1), or apolipoprotein A5 (ApoA-V). Importantly, antibodies against LPL or GPIHBP1 have also been reported to induce autoimmune hyperchylomicronemia.The patient was a 46-year-old man diagnosed with immune thrombocytopenia (ITP) at 41 years. At the time, he was administered prednisolone (PSL) and eltrombopag, a thrombopoietin receptor agonist. At 44 years, he suffered from acute myocardial infarction, and PSL was discontinued to avoid enhancing atherogenic risks. He was maintained on eltrombopag monotherapy. After discontinuing PSL, marked hypertriglyceridemia (3,000 mg/dL) was observed, which did not improve even after a few years of pemafibrate therapy. Upon referral to our clinic, the triglyceride (TG) level was 2,251 mg/dL, ApoC-II was 19.8 mg/dL, LPL was 11.1 ng/mL (0.02-1.5 ng/mL), GPIHBP1 was 47.7 pg/mL (740.0-1,014.0 pg/mL), and anti-GPIHBP1 antibody was detected. The patient was diagnosed to have anti-GPIHBP1 antibody-positive autoimmune hyperchylomicronemia. He was administered PSL 15 mg/day, and TG levels were controlled at approximately 200 mg/dL.Recent studies have reported that patients with anti-GPIHBP1 antibody-induced autoimmune hyperchylomicronemia had concomitant rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's disease, and Graves' disease. We report a rare case of anti-GPIHBP1 antibody-positive autoimmune hyperchylomicronemia with concomitant ITP, which became apparent when PSL was discontinued due to the onset of steroid-induced acute myocardial infarction.
ESTHER : Tanaka_2022_J.Atheroscler.Thromb__
PubMedSearch : Tanaka_2022_J.Atheroscler.Thromb__
PubMedID: 35185060

Title : Whole-body insulin resistance and energy expenditure indices, serum lipids, and skeletal muscle metabolome in a state of lipoprotein lipase overexpression - Nishida_2021_Metabolomics_17_26
Author(s) : Nishida Y , Nishijima K , Yamada Y , Tanaka H , Matsumoto A , Fan J , Uda Y , Tomatsu H , Yamamoto H , Kami K , Kitajima S , Tanaka K
Ref : Metabolomics , 17 :26 , 2021
Abstract : INTRODUCTION: Overexpression of lipoprotein lipase (LPL) protects against high-fat-diet (HFD)-induced obesity and insulin resistance in transgenic rabbits; however, the molecular mechanisms remain unclear. Skeletal muscle is a major organ responsible for insulin-stimulated glucose uptake and energy expenditure. OBJECTIVES: The main purpose of the current study was to examine the effects of the overexpression of LPL on the skeletal muscle metabolomic profiles to test our hypothesis that the mitochondrial oxidative metabolism would be activated in the skeletal muscle of LPL transgenic rabbits and that the higher mitochondrial oxidative metabolism activity would confer better phenotypic metabolic outcomes. METHODS: Under a HFD, insulin resistance index was measured using the intravenous glucose tolerance test, and total energy expenditure (TEE) was measured by doubly-labeled water in control and LPL transgenic rabbits (n = 12, each group). Serum lipids, such as triglycerides and free fatty acid, were also measured. The skeletal muscle metabolite profile was analyzed using capillary electrophoresis time-of flight mass spectrometry in the two groups (n = 9, each group). A metabolite set enrichment analysis (MSEA) with muscle metabolites and a false discovery rate q < 0.2 was performed to identify significantly different metabolic pathways between the 2 groups. RESULTS: The triglycerides and free fatty acid levels and insulin resistance index were lower, whereas the TEE was higher in the LPL transgenic rabbits than in the control rabbits. Among 165 metabolites detected, the levels of 37 muscle metabolites were significantly different between the 2 groups after false discovery rate correction (q < 0.2). The MSEA revealed that the TCA cycle and proteinogenic amino acid metabolism pathways were significantly different between the 2 groups (P < 0.05). In the MSEA, all four selected metabolites for the TCA cycle (2-oxoglutaric acid, citric acid, malic acid, fumaric acid), as well as eight selected metabolites for proteinogenic amino acid metabolism (asparagine, proline, methionine, phenylalanine, histidine, arginine, leucine, isoleucine) were consistently increased in the transgenic rabbits compared with control rabbits, suggesting that these two metabolic pathways were activated in the transgenic rabbits. Some of the selected metabolites, such as citric acid and methionine, were significantly associated with serum lipids and insulin resistance (P < 0.05). CONCLUSION: The current results suggest that the overexpression of LPL may lead to increased activities of TCA cycle and proteinogenic amino acid metabolism pathways in the skeletal muscle, and these enhancements may play an important role in the biological mechanisms underlying the anti-obesity/anti-diabetes features of LPL overexpression.
ESTHER : Nishida_2021_Metabolomics_17_26
PubMedSearch : Nishida_2021_Metabolomics_17_26
PubMedID: 33594546

Title : A Novel Function of Sphingosylphosphorylcholine on the Inhibitory Effects of Acetylcholinesterase Activity - Kitazawa_2021_Biol.Pharm.Bull_44_1717
Author(s) : Kitazawa K , Nagasawa-Shimura N , Tanaka K , Musashi M , Kubota Y , Nagasawa T , Yamaguchi Y
Ref : Biol Pharm Bull , 44 :1717 , 2021
Abstract : Acetylcholine (ACh), a quaternary ammonium cation, is known as one of the itch inducer in atopic dermatitis (AD), an inflammatory skin disease with intense itching. Previous research has reported accumulation of ACh in lesional site of AD patients. Generally, ACh is metabolized by cholinesterase (ChE). Therefore, one of the causes of ACh accumulation may be the suppression of ChE activity. Increased levels of the multifunctional bioactive sphingolipid sphingosylphosphorylcholine (SPC) have also been detected in AD. Since SPC possesses a quaternary ammonium cation, like ACh, it is possible that SPC affects the activity of ChE catalyzing ACh metabolization. We investigated whether SPC influences the activity of ChE by performing enzymatic analysis of ChE in the presence of SPC. We found that SPC strongly suppressed acetylcholinesterase (AChE) activity, but the suppression of butyrylcholinesterase by SPC was quite low. The Michaelis constant (K(m)) of AChE in the presence of SPC increased, and the maximum velocity (V(max)) decreased, indicating that SPC acts as mixed-type inhibitor for AChE. The analysis of SPC analogs clarified the importance of both the quaternary ammonium cation and the carbon chain length of SPC for the AChE inhibitory effect and showed that SPC was unique in AChE inhibition among the sphingolipids in this study. These findings indicate a novel function of SPC on AChE inhibition. Thus, the inhibition activity of SPC may be a factor in the increase of ACh in AD.
ESTHER : Kitazawa_2021_Biol.Pharm.Bull_44_1717
PubMedSearch : Kitazawa_2021_Biol.Pharm.Bull_44_1717
PubMedID: 34719648

Title : Comparative analysis of stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors with neuroprotective and anti-inflammatory activities - Nagumo_2019_Bioorg.Med.Chem.Lett_29_2475
Author(s) : Nagumo M , Ninomiya M , Oshima N , Itoh T , Tanaka K , Nishina A , Koketsu M
Ref : Bioorganic & Medicinal Chemistry Lett , 29 :2475 , 2019
Abstract : Stilbenes and benzofuran neolignans are important groups of plant phenolics therefore they play a significant role in plants and human health. The objective of this study was to investigate the structure-activity relationships of naturally occurring stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors. A series of these compounds were prepared and assessed for their inhibition on acetylcholinesterase activity. delta-Viniferin, pterostilbene trans-dehydrodimer, pallidol, grossamide, and boehmenan exerted acetylcholinesterase inhibitory potential. The several oligomeric compounds protected against cell damage resulting from t-BHP exposure and inhibited lipopolysaccharide/interferon-gamma (LPS/IFNgamma)-induced NO production in vitro. Our findings highlight the great potential of pterostilbene trans-dehydrodimer, pallidol, and boehmenan as multifunctional nutraceuticals for management of neurodegenerative diseases.
ESTHER : Nagumo_2019_Bioorg.Med.Chem.Lett_29_2475
PubMedSearch : Nagumo_2019_Bioorg.Med.Chem.Lett_29_2475
PubMedID: 31350127

Title : Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates - Hara_2018_Nat.Ecol.Evol_2_1761
Author(s) : Hara Y , Yamaguchi K , Onimaru K , Kadota M , Koyanagi M , Keeley SD , Tatsumi K , Tanaka K , Motone F , Kageyama Y , Nozu R , Adachi N , Nishimura O , Nakagawa R , Tanegashima C , Kiyatake I , Matsumoto R , Murakumo K , Nishida K , Terakita A , Kuratani S , Sato K , Hyodo S , Kuraku S
Ref : Nat Ecol Evol , 2 :1761 , 2018
Abstract : Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.
ESTHER : Hara_2018_Nat.Ecol.Evol_2_1761
PubMedSearch : Hara_2018_Nat.Ecol.Evol_2_1761
PubMedID: 30297745
Gene_locus related to this paper: scyto-a0a401nql2 , chipu-a0a401shd8 , chipu-a0a401rzt4 , scyto-a0a401q2n8 , scyto-a0a401nqq7 , chipu-a0a401s2p9 , scyto-a0a401q2m6 , chipu-a0a401rz56

Title : Teneligliptin, a dipeptidyl peptidase-4 inhibitor, attenuated pro-inflammatory phenotype of perivascular adipose tissue and inhibited atherogenesis in normoglycemic apolipoprotein-E-deficient mice - Salim_2017_Vascul.Pharmacol_96-98_19
Author(s) : Salim HM , Fukuda D , Higashikuni Y , Tanaka K , Hirata Y , Yagi S , Soeki T , Shimabukuro M , Sata M
Ref : Vascul Pharmacol , 96-98 :19 , 2017
Abstract : BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0.05), without alteration of blood glucose level or blood pressure. Histological analyses demonstrated that teneligliptin decreased lipid deposition and MCP-1 expression (P<0.05, respectively), and tended to decrease macrophage accumulation in atherosclerotic plaques. The results of quantitative RT-PCR analysis demonstrated that teneligliptin reduced the expression of inflammatory molecules such as TNF-alpha and MCP-1 in the abdominal aorta. Furthermore, teneligliptin reduced the expression of a macrophage marker and Nox-4, a major NADPH oxidase subunit in adipocytes, in PVAT around the aortic arch. Administration of teneligliptin for 8weeks ameliorated endothelium-dependent vasodilation and reduced oxidative stress as determined by urinary 8-OHdG excretion (P<0.05) compared with vehicle. In vitro experiments demonstrated that exendin-4 (Ex-4), a GLP-1 analog, decreased the expression of inflammatory molecules in RAW264.7 cells. Also, Ex-4 decreased Nox4 expression in 3T3-L1 adipocytes. CONCLUSION: Teneligliptin inhibited atherogenesis with attenuation of the inflammatory phenotype in PVAT. A GLP-1 analog suppressed pro-inflammatory activation of macrophages and adipocytes. Suppression of the pro-inflammatory phenotype of PVAT might contribute, at least partially, to the cardioprotective effects of teneligliptin.
ESTHER : Salim_2017_Vascul.Pharmacol_96-98_19
PubMedSearch : Salim_2017_Vascul.Pharmacol_96-98_19
PubMedID: 28347868

Title : gamma-BHC: Its history and mystery--why is only gamma-BHC insecticidal? - Tanaka_2015_Pestic.Biochem.Physiol_120_91
Author(s) : Tanaka K
Ref : Pestic Biochem Physiol , 120 :91 , 2015
Abstract : Among BHC isomers (benzene hexachloride, C6H6Cl6, theoretically eight ones), seven isomers (alpha,beta,gamma,delta,sigma,,) including one racemate (alpha) were isolated and their configurations were elucidated. Among the seven isomers, only gamma-BHC has a potent insecticidal activity. gamma-BHC poisoning symptoms accompanied by the violent tremor of the body, particularly in the legs and abnormal fluttering were consistently correlated with central nervous system effects, and the action was shown on the ganglia rather than on the isolated nerve cord. The excitatory effects of gamma-BHC poisoning on spontaneous activity and synaptic function in the sixth abdominal ganglion of the American cockroach result from the presynaptic action that causes an excessive release of acetylcholine. F. Matsumura found the phenomena of cross resistance between gamma-BHC, cyclodiene insecticides and GABA (gamma-aminobutyric acid) antagonist, picrotoxinin, and concluded that the primary target of gamma-BHC is the picrotoxinin receptor in the GABA receptor Cl- ion channel complex (GABA-gated chloride channel) and its antagonistic action on GABA receptor results in an excessive release of Ach. In order to study the structure-activity relationship, a number of gamma-BHC analogs, in which one or two chlorine atoms on dl or meso position(s) of the gamma-BHC molecule were replaced by various substituents such as hydrogen, halogens other than chlorine and alkoxy groups, etc. were synthesized. In the case of dl type-analogs, there is an optimum volume for dl-substituents, which corresponds to Cl. The question why gamma-BHC is insecticidal and other BHC isomers are not remains unsolved.
ESTHER : Tanaka_2015_Pestic.Biochem.Physiol_120_91
PubMedSearch : Tanaka_2015_Pestic.Biochem.Physiol_120_91
PubMedID: 25987226

Title : Butea superba-Induced Amelioration of Cognitive and Emotional Deficits in Olfactory Bulbectomized Mice and Putative Mechanisms Underlying Its Actions - Mizuki_2014_J.Pharmacol.Sci_124_457
Author(s) : Mizuki D , Qi Z , Tanaka K , Fujiwara H , Ishikawa T , Higuchi Y , Matsumoto K
Ref : J Pharmacol Sci , 124 :457 , 2014
Abstract : This study investigated the effects of alcoholic extract of Butea superba (BS) on cognitive deficits and depression-related behavior using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its actions. OBX mice were treated daily with BS (100 and 300 mg/kg, p.o.) or reference drugs, tacrine (2.5 mg/kg, i.p.) and imipramine (10 mg/kg, i.p.) from day 3 after OBX. OBX impaired non-spatial and spatial cognitive performances, which were elucidated by the novel object recognition test and modified Y maze test, respectively. These deficits were attenuated by tacrine and BS but not imipramine. OBX animals exhibited depression-like behavior in the tail suspension test in a manner reversible by imipramine and BS but not tacrine. OBX down-regulated phosphorylation of synaptic plasticity-related signaling proteins: NMDA receptor, AMPA receptor, calmodulin-dependent kinase II, and cyclic AMP-responsive element-binding protein. OBX also reduced choline acetyltransferase in the hippocampus. BS and tacrine reversed these neurochemical alterations. Moreover, BS inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BS ameliorates not only cognition dysfunction via normalizing synaptic plasticity-related signaling and facilitating central cholinergic systems but also depression-like behavior via a mechanism differing from that implicated in BS amelioration of cognitive function in OBX animals.
ESTHER : Mizuki_2014_J.Pharmacol.Sci_124_457
PubMedSearch : Mizuki_2014_J.Pharmacol.Sci_124_457
PubMedID: 24646653

Title : Expression of adrenergic and cholinergic receptors in murine renal intercalated cells - Jun_2014_J.Vet.Med.Sci_76_1493
Author(s) : Jun JG , Maeda S , Kuwahara-Otani S , Tanaka K , Hayakawa T , Seki M
Ref : J Vet Med Sci , 76 :1493 , 2014
Abstract : Neurons influence renal function and help to regulate fluid homeostasis, blood pressure and ion excretion. Intercalated cells (ICCs) are distributed throughout the renal collecting ducts and help regulate acid/base equilibration. Because ICCs are located among principal cells, it has been difficult to determine the effects that efferent nerve fibers have on this cell population. In this study, we examined the expression of neurotransmitter receptors on the murine renal epithelial M-1 cell line. We found that M-1 cells express a2 and b2 adrenergic receptor mRNA and the b2 receptor protein. Further, b2 receptor-positive cells in the murine cortical collecting ducts also express AQP6, indicating that these cells are ICCs. M-1 cells were found to express m1, m4 and m5 muscarinic receptor mRNAs and the m1 receptor protein. Cells in the collecting ducts also express the m1 receptor protein, and some m1-positive cells express AQP6. Acetylcholinesterase was detected in cortical collecting duct cells. Interestingly, acetylcholinesterase-positive cells neighbored AQP6-positive cells, suggesting that principal cells may regulate the availability of acetylcholine. In conclusion, our data suggest that ICCs in murine renal collecting ducts may be regulated by the adrenergic and cholinergic systems.
ESTHER : Jun_2014_J.Vet.Med.Sci_76_1493
PubMedSearch : Jun_2014_J.Vet.Med.Sci_76_1493
PubMedID: 25069412

Title : Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat - Shimizu_2014_Neuropharmacol_82_19
Author(s) : Shimizu T , Tanaka K , Nakamura K , Taniuchi K , Yawata T , Higashi Y , Ueba T , Dimitriadis F , Shimizu S , Yokotani K , Saito M
Ref : Neuropharmacology , 82 :19 , 2014
Abstract : We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat.
ESTHER : Shimizu_2014_Neuropharmacol_82_19
PubMedSearch : Shimizu_2014_Neuropharmacol_82_19
PubMedID: 24657150

Title : Carlactone is converted to carlactonoic acid by MAX1 in Arabidopsis and its methyl ester can directly interact with AtD14 in vitro - Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
Author(s) : Abe S , Sado A , Tanaka K , Kisugi T , Asami K , Ota S , Kim HI , Yoneyama K , Xie X , Ohnishi T , Seto Y , Yamaguchi S , Akiyama K , Nomura T
Ref : Proc Natl Acad Sci U S A , 111 :18084 , 2014
Abstract : Strigolactones (SLs) stimulate seed germination of root parasitic plants and induce hyphal branching of arbuscular mycorrhizal fungi in the rhizosphere. In addition, they have been classified as a new group of plant hormones essential for shoot branching inhibition. It has been demonstrated thus far that SLs are derived from carotenoid via a biosynthetic precursor carlactone (CL), which is produced by sequential reactions of DWARF27 (D27) enzyme and two carotenoid cleavage dioxygenases CCD7 and CCD8. We previously found an extreme accumulation of CL in the more axillary growth1 (max1) mutant of Arabidopsis, which exhibits increased lateral inflorescences due to SL deficiency, indicating that CL is a probable substrate for MAX1 (CYP711A1), a cytochrome P450 monooxygenase. To elucidate the enzymatic function of MAX1 in SL biosynthesis, we incubated CL with a recombinant MAX1 protein expressed in yeast microsomes. MAX1 catalyzed consecutive oxidations at C-19 of CL to convert the C-19 methyl group into carboxylic acid, 9-desmethyl-9-carboxy-CL [designated as carlactonoic acid (CLA)]. We also identified endogenous CLA and its methyl ester [methyl carlactonoate (MeCLA)] in Arabidopsis plants using LC-MS/MS. Although an exogenous application of either CLA or MeCLA suppressed the growth of lateral inflorescences of the max1 mutant, MeCLA, but not CLA, interacted with Arabidopsis thaliana DWARF14 (AtD14) protein, a putative SL receptor, as shown by differential scanning fluorimetry and hydrolysis activity tests. These results indicate that not only known SLs but also MeCLA are biologically active in inhibiting shoot branching in Arabidopsis.
ESTHER : Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
PubMedSearch : Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
PubMedID: 25425668
Gene_locus related to this paper: arath-AtD14

Title : Chemical profiling with HPLC-FTMS of exogenous and endogenous chemicals susceptible to the administration of chotosan in an animal model of type 2 diabetes-induced dementia - Niu_2014_J.Pharm.Biomed.Anal_104C_21
Author(s) : Niu Y , Li F , Inada C , Tanaka K , Watanabe S , Fujiwara H , Sasaki-Hamada S , Oka JI , Matsumoto K
Ref : J Pharm Biomed Anal , 104C :21 , 2014
Abstract : In our previous study, the daily administration of chotosan (CTS), a Kampo formula consisting of Uncaria and other 10 different crude drugs, ameliorated cognitive deficits in several animal models of dementia including type 2 diabetic db/db mice in a similar manner to tacrine, an acetylcholinesterase inhibitor. The present study investigated the metabonomics of CTS in db/db mice, a type 2 diabetes model, and m/m mice, a non-diabetes control strain, to identify the exogenous and endogenous chemicals susceptible to the administration of CTS using high performance liquid chromatography equipped with an orbitrap hybrid Fourier transform mass spectrometer. The results obtained revealed that the systemic administration of CTS for 20 days led to the distribution of Uncalia plant-derived alkaloids such as rhynchophylline, hirsuteine, and corynoxeine in the plasma and brains of db/db and m/m mice and induced alterations in four major metabolic pathways; i.e., (1) purine, (2) tryptophan, (3) cysteine and methionine, (4) glycerophospholipids in db/db mice. Moreover, glycerophosphocholine (GPC) levels in the plasma and brain were significantly higher in CTS-treated db/db mice than in vehicle-treated control animals. The results of the in vitro experiment using organotypic hippocampal slice cultures demonstrated that GPC (10-30muM), as well as tacrine, protected hippocampal cells from N-methyl-d-aspartate-induced excitotoxicity in a manner that was reversible with the muscarinic receptor antagonist scopolamine, whereas GPC had no effect on the activity of acetylcholinesterase in vitro. Our results demonstrated that some CTS constituents with neuropharmacological activity were distributed in the plasma and brain tissue following the systemic administration of CTS and may subsequently have affected some metabolic pathways including glycerophospholipid metabolism and cognitive function in db/db mice. Moreover, the present metabonomic analysis suggested that GPC is a putative endogenous chemical that may be involved in the tacrine-like actions of CTS in the present diabetic animal model.
ESTHER : Niu_2014_J.Pharm.Biomed.Anal_104C_21
PubMedSearch : Niu_2014_J.Pharm.Biomed.Anal_104C_21
PubMedID: 25459756

Title : Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat - Tanaka_2014_Br.J.Pharmacol_171_202
Author(s) : Tanaka K , Shimizu T , Yanagita T , Nemoto T , Nakamura K , Taniuchi K , Dimitriadis F , Yokotani K , Saito M
Ref : British Journal of Pharmacology , 171 :202 , 2014
Abstract : BACKGROUND AND PURPOSE: Haemopressin and RVD-haemopressin, derived from the haemoglobin alpha-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin-derived peptides on this bombesin-induced response EXPERIMENTAL APPROACH: Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin alpha-positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN, a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. KEY
RESULTS: Bombesin given i.c.v. dose-dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine-induced secretion of catecholamines from chromaffin cells. The bombesin-induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin alpha-positive spinally projecting neurons in the PVN. CONCLUSIONS AND IMPLICATIONS: The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow.
ESTHER : Tanaka_2014_Br.J.Pharmacol_171_202
PubMedSearch : Tanaka_2014_Br.J.Pharmacol_171_202
PubMedID: 24138638

Title : Bacopa monnieri Ameliorates Memory Deficits in Olfactory Bulbectomized Mice: Possible Involvement of Glutamatergic and Cholinergic Systems - Le_2013_Neurochem.Res_38_2201
Author(s) : Le XT , Pham HT , Do PT , Fujiwara H , Tanaka K , Li F , Van Nguyen T , Nguyen KM , Matsumoto K
Ref : Neurochem Res , 38 :2201 , 2013
Abstract : This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.
ESTHER : Le_2013_Neurochem.Res_38_2201
PubMedSearch : Le_2013_Neurochem.Res_38_2201
PubMedID: 23949198

Title : Gene expression in gut symbiotic organ of stinkbug affected by extracellular bacterial symbiont - Futahashi_2013_PLoS.One_8_e64557
Author(s) : Futahashi R , Tanaka K , Tanahashi M , Nikoh N , Kikuchi Y , Lee BL , Fukatsu T
Ref : PLoS ONE , 8 :e64557 , 2013
Abstract : The bean bug Riptortus pedestris possesses a specialized symbiotic organ in a posterior region of the midgut, where numerous crypts harbor extracellular betaproteobacterial symbionts of the genus Burkholderia. Second instar nymphs orally acquire the symbiont from the environment, and the symbiont infection benefits the host by facilitating growth and by occasionally conferring insecticide resistance. Here we performed comparative transcriptomic analyses of insect genes expressed in symbiotic and non-symbiotic regions of the midgut dissected from Burkholderia-infected and uninfected R. pedestris. Expression sequence tag analysis of cDNA libraries and quantitative reverse transcription PCR identified a number of insect genes expressed in symbiosis- or aposymbiosis-associated patterns. For example, genes up-regulated in symbiotic relative to aposymbiotic individuals, including many cysteine-rich secreted protein genes and many cathepsin protease genes, are likely to play a role in regulating the symbiosis. Conversely, genes up-regulated in aposymbiotic relative to symbiotic individuals, including a chicken-type lysozyme gene and a defensin-like protein gene, are possibly involved in regulation of non-symbiotic bacterial infections. Our study presents the first transcriptomic data on gut symbiotic organ of a stinkbug, which provides initial clues to understanding of molecular mechanisms underlying the insect-bacterium gut symbiosis and sheds light on several intriguing commonalities between endocellular and extracellular symbiotic associations.
ESTHER : Futahashi_2013_PLoS.One_8_e64557
PubMedSearch : Futahashi_2013_PLoS.One_8_e64557
PubMedID: 23691247
Gene_locus related to this paper: 9hemi-r4wde3 , 9hemi-r4wpu6

Title : Stimulatory and inhibitory roles of brain 2-arachidonoylglycerol in bombesin-induced central activation of adrenomedullary outflow in rats - Shimizu_2013_J.Pharmacol.Sci_121_157
Author(s) : Shimizu T , Tanaka K , Yokotani K
Ref : J Pharmacol Sci , 121 :157 , 2013
Abstract : 2-Arachidonoylglycerol (2-AG) is recognized as a potent endocannabinoid, which reduces synaptic transmission through cannabinoid CB(1) receptors, and is hydrolyzed by monoacylglycerol lipase (MGL) to arachidonic acid (AA), a cyclooxygenase substrate. We already reported that centrally administered MGL and cyclooxygenase inhibitors each reduced the intracerebroventricularly (i.c.v.) administered bombesin-induced secretion of adrenal catecholamines, while a centrally administered CB(1)-antagonist potentiated the response, indirectly suggesting bidirectional roles of brain 2-AG (stimulatory and inhibitory roles) in the bombesin-induced response. In the present study, we separately examined these bidirectional roles using 2-AG and 2-AG ether (2-AG-E) (stable 2-AG analog for MGL) in rats. 2-AG (0.5 mumol/animal, i.c.v.), but not 2-AG-E (0.5 mumol/animal, i.c.v.), elevated basal plasma catecholamines with JZL184 (MGL inhibitor)- and indomethacin (cyclooxygenase inhibitor)-sensitive brain mechanisms. 2-AG-E (0.1 mumol/animal, i.c.v.) effectively reduced the bombesin (1 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines with rimonabant (CB(1) antagonist)-sensitive brain mechanisms. Immunohistochemical studies demonstrated the bombesin-induced activation of diacylglycerol lipase alpha (2-AG-producing enzyme)-positive spinally projecting neurons in the hypothalamic paraventricular nucleus, a control center of central adrenomedullary outflow. These results directly indicate bidirectional roles of brain 2-AG, a stimulatory role as an AA precursor and an inhibitory role as an endocannabinoid, in the bombesin-induced central adrenomedullary outflow in rats.
ESTHER : Shimizu_2013_J.Pharmacol.Sci_121_157
PubMedSearch : Shimizu_2013_J.Pharmacol.Sci_121_157
PubMedID: 23386378

Title : Low NDRG1 mRNA expression predicts a poor prognosis in neuroblastoma patients - Matsushita_2013_Pediatr.Surg.Int_29_363
Author(s) : Matsushita K , Uchida K , Saigusa S , Ide S , Hashimoto K , Koike Y , Otake K , Inoue M , Tanaka K , Kusunoki M
Ref : Pediatr Surg Int , 29 :363 , 2013
Abstract : PURPOSE: N-myc downstream regulated gene 1 (NDRG1) markedly reduces metastasis of numerous tumors. However, NDRG1's function in malignant tumors has not been fully determined. Therefore, we investigated the association of NDRG1 expression with clinical outcomes in neuroblastoma (NB) patients.
METHODS: We obtained total RNA from residual cancer cells using microdissection from NB patients. Furthermore, we examined the expression of NDRG1 in NB patients using immunohistochemical staining.
RESULTS: Of the 48 patients observed, low NDRG1 expression was associated with poor prognostic factors such as primary tumor size and MYCN amplification. Low expression of NDRG1 was associated with a poor prognosis (p = 0.001) and multivariate analysis identified low expression of NDRG1 as an independent risk factor for predicting poor prognosis in NB patients. Furthermore, in the MYCN non-amplification group (n = 33), low expression of NDRG1 was associated with a poor prognosis (p = 0.001). Immunohistochemical analysis showed NDRG1 expression at the plasma membranes of NB cells. NDRG1 expression levels were also correlated with expression of NDRG1 mRNA. CONCLUSION: We confirmed that low NDRG1 expression is a significant and independent prognostic indicator in NB by multivariate analysis. Furthermore, NDRG1 may be a novel prognostic marker in MYCN non-amplification NB patients.
ESTHER : Matsushita_2013_Pediatr.Surg.Int_29_363
PubMedSearch : Matsushita_2013_Pediatr.Surg.Int_29_363
PubMedID: 23296375

Title : Draft Genome Sequence of Holospora undulata Strain HU1, a Micronucleus-Specific Symbiont of the Ciliate Paramecium caudatum - Dohra_2013_Genome.Announc_1_E00664
Author(s) : Dohra H , Suzuki H , Suzuki T , Tanaka K , Fujishima M
Ref : Genome Announc , 1 : , 2013
Abstract : Holospora undulata is a micronucleus-specific symbiont of the ciliate Paramecium caudatum. We report here the draft genome sequence of H. undulata strain HU1. This genome information will contribute to the study of symbiosis between H. undulata and the host P. caudatum.
ESTHER : Dohra_2013_Genome.Announc_1_E00664
PubMedSearch : Dohra_2013_Genome.Announc_1_E00664
PubMedID: 23969064
Gene_locus related to this paper: 9prot-a0a061jga0 , 9prot-a0a061jg10

Title : Clinical implications of CES2 RNA expression in neuroblastoma - Uchida_2013_J.Pediatr.Surg_48_502
Author(s) : Uchida K , Otake K , Tanaka K , Hashimoto K , Saigusa S , Matsushita K , Koike Y , Inoue M , Ueeda M , Okugawa Y , Inoue Y , Mohri Y , Kusunoki M
Ref : J Pediatr Surg , 48 :502 , 2013
Abstract : BACKGROUND/PURPOSE: Human carboxylesterase 2 (CES2) is the key enzyme for metabolic activation of irinotecan (CPT-11). The aim was to evaluate the clinical implications of CES2 RNA expression in neuroblastoma cells.
METHODS: CES2 RNA expression was determined by real-time reverse transcription-polymerase chain reaction in five neuroblastoma cell lines and 42 clinical samples of untreated neuroblastoma. Sensitivity to CPT-11 was assessed by WST-8 colorimetric assays. Induction of apoptosis was evaluated by flow cytometry after CPT-11 exposure. Protein expression of CES2 was evaluated by Western blotting analysis. CES2 RNA expression in clinical samples was investigated for its associations with the clinicopathological characteristics.
RESULTS: CES2 RNA expression was observed in neuroblastoma cells, and its expression in neuroblastoma cell lines was positively correlated with sensitivity to CPT-11 and apoptosis after CPT-11 exposure in vitro. CES2 RNA expression was correlated with the protein levels of CES2 in vitro. CES2 RNA expression was significantly higher in patients with a characteristic related to advanced disease.
CONCLUSIONS: Our results suggest the potential of clinical application of CPT-11 in neuroblastoma treatment for patients with advanced disease.
ESTHER : Uchida_2013_J.Pediatr.Surg_48_502
PubMedSearch : Uchida_2013_J.Pediatr.Surg_48_502
PubMedID: 23480903

Title : Brain phospholipase C, diacylglycerol lipase and monoacylglycerol lipase are involved in (+\/-)-epibatidine-induced activation of central adrenomedullary outflow in rats - Shimizu_2012_Eur.J.Pharmacol_691_93
Author(s) : Shimizu T , Tanaka K , Nakamura K , Taniuchi K , Yokotani K
Ref : European Journal of Pharmacology , 691 :93 , 2012
Abstract : We previously reported that intracerebroventricularly (i.c.v.) administered (+/-)-epibatidine (a potent agonist of nicotinic acetylcholine receptors) (1, 5 and 10 nmol/animal) dose-dependently elevated plasma levels of noradrenaline and adrenaline and that this response was reduced by i.c.v. administered indomethacin (cyclooxygenase inhibitor) and abolished by bilateral adrenalectomy, indicating the involvement of brain arachidonic acid, as a substrate of cyclooxygenase, in this alkaloid-induced secretion of both catecholamines from the adrenal medulla in rats. Arachidonic acid is mainly released by the action of phospholipase A(2), but is also released by a phospholipase C-, diacylglycerol lipase- and monoacylglycerol lipase-mediated pathway. In the present study, (+/-)-epibatidine (5 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was not influenced by pretreatment with mepacrine (phospholipase A(2) inhibitor) (1.1 and 2.2 mumol/animal, i.c.v.), but was effectively reduced by pretreatment with U-73122 (1-[6-[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) (phospholipase C inhibitor) (10 and 30 nmol/animal, i.c.v.), RHC-80267 [1,6-bis(cyclohexyloximinocarbonylamino)hexane] (diacylglycerol lipase inhibitor) (1.3 and 2.6 mumol/animal, i.c.v.), MAFP (methyl arachidonoyl fluorophosphonate) (monoacylglycerol lipase inhibitor) (0.7 and 1.4 mumol/animal, i.c.v.) or JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (selective monoacylglycerol lipase inhibitor) (0.7 and 1.4 mumol/animal, i.c.v.). Immunohistochemical studies demonstrated that (+/-)-epibatidine (10 nmol/animal, i.c.v.) activates spinally projecting neurons expressing monoacylglycerol lipase in the rat hypothalamic paraventricular nucleus, a control center of central sympatho-adrenomedullary outflow. Taken together, the brain phospholipase C-, diacylglycerol lipase- and monoacylglycerol lipase-mediated pathway seems to be involved in the centrally administered (+/-)-epibatidine-induced activation of central adrenomedullary outflow in rats.
ESTHER : Shimizu_2012_Eur.J.Pharmacol_691_93
PubMedSearch : Shimizu_2012_Eur.J.Pharmacol_691_93
PubMedID: 22796670

Title : Iodide oxidation by a novel multicopper oxidase from the alphaproteobacterium strain Q-1 - Suzuki_2012_Appl.Environ.Microbiol_78_3941
Author(s) : Suzuki M , Eda Y , Ohsawa S , Kanesaki Y , Yoshikawa H , Tanaka K , Muramatsu Y , Yoshikawa J , Sato I , Fujii T , Amachi S
Ref : Applied Environmental Microbiology , 78 :3941 , 2012
Abstract : Alphaproteobacterium strain Q-1 is able to oxidize iodide (I(-)) to molecular iodine (I(2)) by an oxidase-like enzyme. One of the two isoforms of the iodide-oxidizing enzyme (IOE-II) produced by this strain was excised from a native polyacrylamide gel, eluted, and purified. IOE-II appeared as a single band (51 kDa) and showed significant in-gel iodide-oxidizing activity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis without heat treatment. However, at least two bands with much higher molecular masses (150 and 230 kDa) were observed with heat treatment (95 degrees C, 3 min). IOE-II was inhibited by NaN(3), KCN, EDTA, and a copper chelator, o-phenanthroline. In addition to iodide, IOE-II showed significant activities toward phenolic compounds such as syringaldazine, 2,6-dimethoxy phenol, and p-phenylenediamine. IOE-II contained copper atoms as prosthetic groups and had UV/VIS absorption peaks at 320 and 590 nm. Comparison of several internal amino acid sequences obtained from trypsin-digested IOE-II with a draft genome sequence of strain Q-1 revealed that the products of two open reading frames (IoxA and IoxC), with predicted molecular masses of 62 and 71 kDa, are involved in iodide oxidation. Furthermore, subsequent tandem mass spectrometric analysis repeatedly detected peptides from IoxA and IoxC with high sequence coverage (32 to 40%). IoxA showed homology with the family of multicopper oxidases and included four copper-binding regions that are highly conserved among various multicopper oxidases. These results suggest that IOE-II is a multicopper oxidase and that it may occur as a multimeric complex in which at least two proteins (IoxA and IoxC) are associated.
ESTHER : Suzuki_2012_Appl.Environ.Microbiol_78_3941
PubMedSearch : Suzuki_2012_Appl.Environ.Microbiol_78_3941
PubMedID: 22447601
Gene_locus related to this paper: 9prot-a0a061qis2 , 9prot-a0a061q8k2 , 9prot-a0a061qhj5

Title : Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice - Yamada_2011_J.Ethnopharmacol_135_737
Author(s) : Yamada M , Hayashida M , Zhao Q , Shibahara N , Tanaka K , Miyata T , Matsumoto K
Ref : J Ethnopharmacol , 135 :737 , 2011
Abstract : AIM OF THE STUDY: Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). MATERIALS AND METHODS: OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. RESULTS: OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M(1) receptor expression without affecting muscarinic M(3) receptor expression or AChE activity. CONCLUSION: These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.
ESTHER : Yamada_2011_J.Ethnopharmacol_135_737
PubMedSearch : Yamada_2011_J.Ethnopharmacol_135_737
PubMedID: 21513784

Title : Prognostic significance of host- and tumor-related factors in patients with gastric cancer - Mohri_2010_World.J.Surg_34_285
Author(s) : Mohri Y , Tanaka K , Ohi M , Yokoe T , Miki C , Kusunoki M
Ref : World J Surg , 34 :285 , 2010
Abstract : BACKGROUND: Various factors regarding the biological state of tumors or the nutritional status of patients have been reported individually to correlate with prognosis. Identification of defined patient groups based on a prognostic score may improve the prediction of survival and individualization of therapy. The aim of the present study was to identify clinically useful parameters obtainable before treatment that could be used for predicting clinical outcomes in patients with gastric cancer. METHODS: In 357 consecutive patients who had been treated for potentially curable gastric cancer, we retrospectively analyzed the following clinicopathological factors: sex, age, body mass index, body weight changes, hemoglobin, white blood cell count, neutrophil to lymphocyte (N/L) ratio, serum C-reactive protein (CRP), serum albumin, serum cholinesterase, tumor location, tumor size, histology, and clinical tumor node metastasis (TNM) stage. Factors related to prognosis were evaluated by univariate and multivariate analysis. RESULTS: From univariate analysis, significant differences in survival were found for age, hemoglobin, N/L ratio, serum CRP, serum albumin, serum cholinesterase, tumor size, and clinical T and N grouping. N/L ratio, tumor size, and clinical T grouping were identified as independent prognostic indicators in multivariate analysis. A prognostic score was constructed using these variables to estimate the probability of death. The model gave an area under the receiver operating characteristic curve of 0.85 for prediction of death at 5 years. CONCLUSIONS: This model based on N/L ratio, tumor size, and clinical T grouping before treatment offers a very informative scoring system for predicting prognosis of gastric cancer.
ESTHER : Mohri_2010_World.J.Surg_34_285
PubMedSearch : Mohri_2010_World.J.Surg_34_285
PubMedID: 19997918

Title : Pre-heparin serum lipoprotein lipase concentrations in obese men of contrasting physical activity status: a preliminary study -
Author(s) : Miyashita M , Eto M , Sasai H , Tsujimoto T , So R , Nomata Y , Tanaka K
Ref : J Atheroscler Thromb , 17 :1110 , 2010
PubMedID: 20585191

Title : Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population - Hotta_2010_J.Hum.Genet_55_738
Author(s) : Hotta K , Nakamura M , Nakamura T , Matsuo T , Nakata Y , Kamohara S , Miyatake N , Kotani K , Komatsu R , Itoh N , Mineo I , Wada J , Yoneda M , Nakajima A , Funahashi T , Miyazaki S , Tokunaga K , Kawamoto M , Masuzaki H , Ueno T , Hamaguchi K , Tanaka K , Yamada K , Hanafusa T , Oikawa S , Yoshimatsu H , Nakao K , Sakata T , Matsuzawa Y , Nakamura Y , Kamatani N
Ref : J Hum Genet , 55 :738 , 2010
Abstract : The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian population are associated with variations in several genes, including neurexin 3 (NRXN3), transcription factor AP-2beta (TFAP2B), methionine sulfoxide reductase A (MSRA), lysophospholipase-like-1 (LYPLAL1), fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes. To investigate the relationship between VFA and subcutaneous fat area (SFA) and these genes in the recruited Japanese population, we genotyped 8 single-nucleotide polymorphisms (SNPs) in these 6 genes from 1228 subjects. Multiple regression analysis revealed that gender, age, and rs1558902 and rs1421085 genotypes (additive model) in FTO were significantly associated with body mass index (BMI; P=0.0039 and 0.0039, respectively), SFA (P=0.0027 and 0.0023, respectively) and VFA (P=0.045 and 0.040, respectively). However, SNPs in other genes, namely, NRXN3, TFAP2B, MSRA, LYPLAL1 and MC4R were not significantly associated with BMI, SFA or VFA. Our data suggest that some SNPs, which were identified in genome-wide studies in the Caucasians, also confer susceptibility to fat distribution in the Japanese subjects.
ESTHER : Hotta_2010_J.Hum.Genet_55_738
PubMedSearch : Hotta_2010_J.Hum.Genet_55_738
PubMedID: 20703240

Title : Living donor liver transplantation for Dorfman-Chanarin syndrome with 1 year follow-up: case report - Takeda_2010_Transplant.Proc_42_3858
Author(s) : Takeda K , Tanaka K , Kumamoto T , Morioka D , Endo I , Togo S , Shimada H
Ref : Transplant Proc , 42 :3858 , 2010
Abstract : A 27-year-old Japanese man underwent liver transplantation because of uncompensated cirrhosis due to Dorfman-Chanarin syndrome (DCS). At birth, the patient displayed ichthyosis and liver dysfunction. Moreover, mental retardation appeared and intracytoplasmic vacuoles were observed within peripheral blood neutrophils. A fatty liver was also noticed, leading to the diagnosis of DCS. When he was referred to our hospital, his American Society of Anesthesiologists score was 3. The findings of computed tomography showed liver atrophy, splenomegaly, and ascites. The Child-Pugh score was B, and the Model for End-stage Liver Disease score was 14. The pathophysiology was DCS with uncompensated liver cirrhosis. Therefore, living donor liver transplantation (LDLT) was performed from the patient's brother. The histological appearance of the resected liver revealed macrovesicular steatosis in most hepatocytes with excess fibrous tissue in the portal areas. These findings were compatible with nonalcoholic steatohepatitis. Although the patient's mental retardation and characteristic appearance have not improved, good liver function has been maintained since LDLT. An outpatient protocol liver biopsy performed at 12 months after LDLT did not show recurrence of macrovesicular steatosis.
ESTHER : Takeda_2010_Transplant.Proc_42_3858
PubMedSearch : Takeda_2010_Transplant.Proc_42_3858
PubMedID: 21094870
Gene_locus related to this paper: human-ABHD5

Title : Twelve-week jogging training increases pre-heparin serum lipoprotein lipase concentrations in overweight\/obese middle-aged men - Miyashita_2010_J.Atheroscler.Thromb_17_21
Author(s) : Miyashita M , Eto M , Sasai H , Tsujimoto T , Nomata Y , Tanaka K
Ref : J Atheroscler Thromb , 17 :21 , 2010
Abstract : AIM: Enhancement of lipoprotein lipase (LPL) activity through drug administration has been shown to increase pre-heparin serum LPL concentrations; however, pre-heparin serum LPL responses to exercise training have not been determined. The present study was undertaken to investigate the effects of 12 weeks of supervised aerobic exercise training on pre-heparin serum LPL concentrations in overweight/obese men. METHODS: Fifteen overweight/obese middle-aged men were assigned to one of two 12-week supervised exercise interventions: a walking group (eight participants gradually increasing brisk walking to 60 min/day 3 days a week) or a jogging group (seven participants gradually increasing jogging to 60 min/day 3 days a week). All participants maintained ad libitum diets. Blood samples were collected at baseline and immediately after 12 weeks. The primary outcome was pre-heparin serum LPL. RESULTS: Pre-heparin serum LPL concentrations were increased in the jogging group after 12 weeks compared with the baseline values (mean+/-SEM: 37.6+/-4.7 vs. 51.0+/-6.6 ng/mL, respectively, p= 0.033). In the walking group, pre-heparin serum LPL concentrations remained unchanged after 12 weeks. CONCLUSIONS: This study demonstrates that 12 weeks of jogging training increases pre-heparin serum LPL concentrations in overweight/obese middle-aged men.
ESTHER : Miyashita_2010_J.Atheroscler.Thromb_17_21
PubMedSearch : Miyashita_2010_J.Atheroscler.Thromb_17_21
PubMedID: 20075597

Title : Acetylcholinesterase activity, choline acetyltransferase and vesicular acetylcholine transporter immunoreactivities in the rat adrenal gland during postnatal development - Murabayashi_2009_Anat.Rec.(Hoboken)_292_371
Author(s) : Murabayashi H , Kuramoto H , Ishikawa K , Iwamoto J , Miyakawa K , Tanaka K , Sekikawa M , Sasaki M , Kitamura N , Oomori Y
Ref : Anatomical Record (Hoboken) , 292 :371 , 2009
Abstract : From postnatal-day-0 to postnatal-day-2, a few acetylcholinesterase (AChE)-active and choline acetytransferase (ChAT)-immunoreactive nerve fibers and relatively numerous vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were observed in the rat adrenal medulla. Despite relatively numerous clear vesicles in the nerve fibers, the synthesis and hydrolysis of acetylcholine may not be fully activated until postnatal-day-2. The number of AChE-active and ChAT-immunoreactive nerve fibers dramatically increased and that of VAChT-immunoreactive puncta gradually increased from postnatal-day-3 to postnatal-week-1. The synthesis and hydrolysis of acetylcholine may be dramatically activated in the nerve fibers of the medulla until postnatal-week-1. From postnatal-week-2 to postnatal-week-3, the number of AChE-active and the ChAT-immunoreactive nerve fibers gradually increased and reached the adult levels. The VAChT-immunoreactive puncta per unit area was maximum number at postnatal-week-2. The synthesis and hydrolysis of acetylcholine in the nerve fibers of the medulla may be completed between postnatal-week-2 to postnatal-week-3. The diameter of the VAChT-immunoreactive puncta gradually increased from postnatal-day-0 with aging. However, the number of the VAChT-immunoreactive puncta gradually decreased from postnatal-week-2 onwards. In electron-microscopy, the VAChT-immunoreactive deposits were seen in clusters of clear vesicles, and the diameter of the nerve fibers and the number of clear vesicles at postnatal-week-8 increased compared with those at postnatal-week-2. The AChE-active, ChAT-immunoreactive, and VAChT-immunoreactive nerve fibers observed around noradrenaline (NA) cells were denser than those around adrenaline (A) cells in the medulla at postnatal-week-8. These suggest that the preferential innervation of NA and A cells may cause the differential secretion NA and A.
ESTHER : Murabayashi_2009_Anat.Rec.(Hoboken)_292_371
PubMedSearch : Murabayashi_2009_Anat.Rec.(Hoboken)_292_371
PubMedID: 19248156

Title : Effects of galantamine on L-NAME-induced behavioral impairment in Y-maze task in mice - Tanaka_2009_Neurosci.Lett_462_235
Author(s) : Tanaka K , Yagi T , Shimakoshi R , Azuma K , Nanba T , Ogo H , Tamura A , Asanuma M
Ref : Neuroscience Letters , 462 :235 , 2009
Abstract : Nitric oxide (NO) may play a role in the established processes of learning and memory. We examined the effects of N(omega)-nitro-L-arginine methylester (L-NAME), a nonselective inhibitor of NO synthase (NOS), on the performance of mice in a Y-maze task. L-NAME (100 mg/kg) markedly impaired spontaneous alternation behavior. However, galantamine (0.5 mg/kg) significantly attenuated this l-NAME-induced impairment. To clarify the molecular basis underlying galantamine's protective effects against L-NAME-induced impairment of spontaneous alternation behavior, we tested the ability of mecamylamine, an antagonist of nicotinic ACh receptor (nAChR), and scopolamine, an antagonist of muscarinic ACh receptor, to reduce galantamine's protective effects, and found that only the former had such an ability. Galantamine significantly also reduced L-NAME-induced decreases in NOx levels. However, mecamylamine cancelled galantamine's efficacy in countering the L-NAME-induced decrease in NOx levels. In the present study, we have determined that galantamine's protection against L-NAME-induced impairment of spontaneous alternation behavior in the Y-maze task might be mediated mainly by NOergic activation via the nAChR-related pathway.
ESTHER : Tanaka_2009_Neurosci.Lett_462_235
PubMedSearch : Tanaka_2009_Neurosci.Lett_462_235
PubMedID: 19615429

Title : Serum immunosuppressive acidic protein reflects systemic deterioration of colorectal cancer patient condition - Toiyama_2008_J.Surg.Oncol_97_404
Author(s) : Toiyama Y , Miki C , Inoue Y , Okugawa Y , Koike Y , Watanabe H , Yokoe T , Hiro J , Ojima E , Tanaka K , Kusunoki M
Ref : J Surg Oncol , 97 :404 , 2008
Abstract : AIMS: Immunosuppressive acidic protein (IAP) is a potent biological marker for immunological surveillance in patients with malignant tumors. This study aimed to investigate the significance of serum IAP as an index of disease status, clinicopathological findings and prognosis in colorectal cancer. METHODS: A total of 101 patients with colorectal cancer and 80 normal volunteers were included in this retrospective trial. Preoperative serum IAP was assayed using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: The serum IAP level in the patients, which was not associated with clinicopathological features except for tumor size, was significantly higher than that in controls. The serum IAP level was closely correlated with percent body weight loss, serum albumin and cholinesterase, and percentage of circulating lymphocytes reflecting the host's nutritional and immunological conditions. Interestingly, these parameters were not associated with factors reflecting disease progression except for tumor size. The prognosis of patients with higher IAP levels was significantly worse than that of patients with lower IAP levels. Furthermore, an elevated serum IAP level was an independent prognostic marker in all patients. CONCLUSION: The preoperative serum IAP level may reflect the general condition of colorectal cancer patients, and thus may predict long-term survival independently of stage progression.
ESTHER : Toiyama_2008_J.Surg.Oncol_97_404
PubMedSearch : Toiyama_2008_J.Surg.Oncol_97_404
PubMedID: 18181167

Title : [Generation of mice with glial cell dysfunction] - Tanaka_2007_Brain.Nerve_59_747
Author(s) : Tanaka K , Lee HU , Ikenaka K
Ref : Brain Nerve , 59 :747 , 2007
Abstract : To examine astrocytic function, we have developed model mice harboring astrocyte-specific disease causal gene and tried to examine astrocytic function in vivo. Alexander disease, megalencephalic leukodystrophy with subcortical cysts (MLC), and autistic spectrum disorder with neuroligin 3/4 mutations are known to be astrocyte-specific disease so far. First of all, we have established Alexander disease model mouse. Alexander disease is caused by coding mutation in glial fibrillary acidic protein (GFAP) and mutant GFAP forms inclusion bodies, called Rosenthal fibers, in astrocytes. Its pathophysiology is still unknown. We generated transgenic mice that express human GFAP R239H mutant under the control of mouse GFAP promoter. Lines with single copy exhibited weak human GFAP expression in astrocytes that did not produce aggregates despite the existence of mutation, whereas lines with multi copies exhibited strong expression and the formation of aggregates, starting at P14. The line with aggregates showed higher sensitivity to kainate than the line without them, whose sensitivity was not different from the wild type mouse, suggesting that the presence of GFAP aggregates but not the presence of mutant GFAP altered the sensitivity. Changes in several electrophysiological parameters, including facilitation of LTP, were also observed in this model mouse. We believe that this transgenic line is a useful tool to study astrocytic function in vivo.
ESTHER : Tanaka_2007_Brain.Nerve_59_747
PubMedSearch : Tanaka_2007_Brain.Nerve_59_747
PubMedID: 17663146

Title : A 100\%-complete sequence reveals unusually simple genomic features in the hot-spring red alga Cyanidioschyzon merolae - Nozaki_2007_BMC.Biol_5_28
Author(s) : Nozaki H , Takano H , Misumi O , Terasawa K , Matsuzaki M , Maruyama S , Nishida K , Yagisawa F , Yoshida Y , Fujiwara T , Takio S , Tamura K , Chung SJ , Nakamura S , Kuroiwa H , Tanaka K , Sato N , Kuroiwa T
Ref : BMC Biol , 5 :28 , 2007
Abstract : BACKGROUND: All previously reported eukaryotic nuclear genome sequences have been incomplete, especially in highly repeated units and chromosomal ends. Because repetitive DNA is important for many aspects of biology, complete chromosomal structures are fundamental for understanding eukaryotic cells. Our earlier, nearly complete genome sequence of the hot-spring red alga Cyanidioschyzon merolae revealed several unique features, including just three ribosomal DNA copies, very few introns, and a small total number of genes. However, because the exact structures of certain functionally important repeated elements remained ambiguous, that sequence was not complete. Obviously, those ambiguities needed to be resolved before the unique features of the C. merolae genome could be summarized, and the ambiguities could only be resolved by completing the sequence. Therefore, we aimed to complete all previous gaps and sequence all remaining chromosomal ends, and now report the first nuclear-genome sequence for any eukaryote that is 100% complete.
RESULTS: Our present complete sequence consists of 16546747 nucleotides covering 100% of the 20 linear chromosomes from telomere to telomere, representing the simple and unique chromosomal structures of the eukaryotic cell. We have unambiguously established that the C. merolae genome contains the smallest known histone-gene cluster, a unique telomeric repeat for all chromosomal ends, and an extremely low number of transposons. CONCLUSION: By virtue of these attributes and others that we had discovered previously, C. merolae appears to have the simplest nuclear genome of the non-symbiotic eukaryotes. These unusually simple genomic features in the 100% complete genome sequence of C. merolae are extremely useful for further studies of eukaryotic cells.
ESTHER : Nozaki_2007_BMC.Biol_5_28
PubMedSearch : Nozaki_2007_BMC.Biol_5_28
PubMedID: 17623057
Gene_locus related to this paper: cyam1-m1vi61 , cyam1-m1vhh9

Title : Noninvasive evaluation of graft steatosis in living donor liver transplantation - Iwasaki_2004_Transplantation_78_1501
Author(s) : Iwasaki M , Takada Y , Hayashi M , Minamiguchi S , Haga H , Maetani Y , Fujii K , Kiuchi T , Tanaka K
Ref : Transplantation , 78 :1501 , 2004
Abstract : BACKGROUND: Hepatic steatosis affects graft function as well as postoperative recovery of donors in living donor liver transplantation. Liver macrovesicular steatosis in living donors was assessed using quantitative X-ray computed tomography (CT) analysis and histological examination of intraoperative liver biopsy.
METHODS: A total of 266 living donors with complete pretransplant CT data and intraoperative "time 0" biopsy were included in the study. Liver biopsy specimen obtained during donor operation was examined for macrovesicular steatosis and was classified as none; mild (<30%); moderate (30%-60%); or severe (>60%). Liver-to-spleen CT attenuation values ratio (L/S ratio) on noncontrast-CT was evaluated for its usefulness as an index of hepatic steatosis in comparison with other parameters including body mass index (BMI) and serum liver function tests (gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, and total cholesterol) using receiver operating characteristic (ROC) analysis. RESULTS.: Histological grade of macrovesicular steatosis was none in 198 patients (74.4%), mild in 50 (18.8%), moderate in 15 (5.7%), and severe in 3 (1.1%). The median L/S ratios for the respective histological grades were 1.20 (range: 1.00-1.46), 1.12 (0.83-1.37), 1.01 (0.74-1.21), and 0.90 (0.70-0.99) (P<0.0001). The ROC curve for L/S ratio was located closest to the upper left corner, and the area under the curve of L/S ratio was significantly larger than that of any other preoperative variables. CONCLUSION: L/S ratio calculated from preoperative CT can be a useful tool to discriminate hepatic macrovesicular steatosis. Based on the present results, the optimal cut-off value for L/S ratio to exclude more than moderate steatosis would be 1.1.
ESTHER : Iwasaki_2004_Transplantation_78_1501
PubMedSearch : Iwasaki_2004_Transplantation_78_1501
PubMedID: 15599315

Title : Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D - Matsuzaki_2004_Nature_428_653
Author(s) : Matsuzaki M , Misumi O , Shin IT , Maruyama S , Takahara M , Miyagishima SY , Mori T , Nishida K , Yagisawa F , Yoshida Y , Nishimura Y , Nakao S , Kobayashi T , Momoyama Y , Higashiyama T , Minoda A , Sano M , Nomoto H , Oishi K , Hayashi H , Ohta F , Nishizaka S , Haga S , Miura S , Morishita T , Kabeya Y , Terasawa K , Suzuki Y , Ishii Y , Asakawa S , Takano H , Ohta N , Kuroiwa H , Tanaka K , Shimizu N , Sugano S , Sato N , Nozaki H , Ogasawara N , Kohara Y , Kuroiwa T
Ref : Nature , 428 :653 , 2004
Abstract : Small, compact genomes of ultrasmall unicellular algae provide information on the basic and essential genes that support the lives of photosynthetic eukaryotes, including higher plants. Here we report the 16,520,305-base-pair sequence of the 20 chromosomes of the unicellular red alga Cyanidioschyzon merolae 10D as the first complete algal genome. We identified 5,331 genes in total, of which at least 86.3% were expressed. Unique characteristics of this genomic structure include: a lack of introns in all but 26 genes; only three copies of ribosomal DNA units that maintain the nucleolus; and two dynamin genes that are involved only in the division of mitochondria and plastids. The conserved mosaic origin of Calvin cycle enzymes in this red alga and in green plants supports the hypothesis of the existence of single primary plastid endosymbiosis. The lack of a myosin gene, in addition to the unexpressed actin gene, suggests a simpler system of cytokinesis. These results indicate that the C. merolae genome provides a model system with a simple gene composition for studying the origin, evolution and fundamental mechanisms of eukaryotic cells.
ESTHER : Matsuzaki_2004_Nature_428_653
PubMedSearch : Matsuzaki_2004_Nature_428_653
PubMedID: 15071595
Gene_locus related to this paper: cyam1-m1vi61 , cyam1-m1vhh9

Title : Pesticide residues in food acute dietary exposure - Hamilton_2004_Pest.Manag.Sci_60_311
Author(s) : Hamilton D , Ambrus , Dieterle R , Felsot A , Harris C , Petersen B , Racke K , Wong S-S , Gonzalez R , Tanaka K , Earl M , Roberts G , Bhula R
Ref : Pest Manag Sci , 60 :311 , 2004
Abstract : Consumer risk assessment is a crucial step in the regulatory approval of pesticide use on food crops. Recently, an additional hurdle has been added to the formal consumer risk assessment process with the introduction of short-term intake or exposure assessment and a comparable short-term toxicity reference, the acute reference dose. Exposure to residues during one meal or over one day is important for short-term or acute intake. Exposure in the short term can be substantially higher than average because the consumption of a food on a single occasion can be very large compared with typical long-term or mean consumption and the food may have a much larger residue than average. Furthermore, the residue level in a single unit of a fruit or vegetable may be higher by a factor (defined as the variability factor, which we have shown to be typically x3 for the 97.5th percentile unit) than the average residue in the lot. Available marketplace data and supervised residue trial data are examined in an investigation of the variability of residues in units of fruit and vegetables. A method is described for estimating the 97.5th percentile value from sets of unit residue data. Variability appears to be generally independent of the pesticide, the crop, crop unit size and the residue level. The deposition of pesticide on the individual unit during application is probably the most significant factor. The diets used in the calculations ideally come from individual and household surveys with enough consumers of each specific food to determine large portion sizes. The diets should distinguish the different forms of a food consumed, eg canned, frozen or fresh, because the residue levels associated with the different forms may be quite different. Dietary intakes may be calculated by a deterministic method or a probabilistic method. In the deterministic method the intake is estimated with the assumptions of large portion consumption of a 'high residue' food (high residue in the sense that the pesticide was used at the highest recommended label rate, the crop was harvested at the smallest interval after treatment and the residue in the edible portion was the highest found in any of the supervised trials in line with these use conditions). The deterministic calculation also includes a variability factor for those foods consumed as units (eg apples, carrots) to allow for the elevated residue in some single units which may not be seen in composited samples. In the probabilistic method the distribution of dietary consumption and the distribution of possible residues are combined in repeated probabilistic calculations to yield a distribution of possible residue intakes. Additional information such as percentage commodity treated and combination of residues from multiple commodities may be incorporated into probabilistic calculations. The IUPAC Advisory Committee on Crop Protection Chemistry has made 11 recommendations relating to acute dietary exposure.
ESTHER : Hamilton_2004_Pest.Manag.Sci_60_311
PubMedSearch : Hamilton_2004_Pest.Manag.Sci_60_311
PubMedID: 15119595

Title : Effect of donepezil on group II mGlu receptor agonist- or antagonist-induced amnesia on passive avoidance in mice - Sato_2003_Neural.Plast_10_319
Author(s) : Sato T , Tanaka K , Ohnishi Y , Irifune M , Nishikawa T
Ref : Neural Plast , 10 :319 , 2003
Abstract : We examined the effect of the acetylcholinesterase (AChE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency. The results suggest that activation of group II mGlu receptors and disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor antagonist) have a negative action on step-through passive avoidance memory performance, and that group II mGlu receptors and ACh interact to modulate learning and memory function.
ESTHER : Sato_2003_Neural.Plast_10_319
PubMedSearch : Sato_2003_Neural.Plast_10_319
PubMedID: 15152985

Title : Identification and biochemical characterization of plant acylamino acid-releasing enzyme - Yamauchi_2003_J.Biochem_134_251
Author(s) : Yamauchi Y , Ejiri Y , Toyoda Y , Tanaka K
Ref : J Biochem , 134 :251 , 2003
Abstract : Plant acylamino acid-releasing enzyme (AARE) catalyzing the N-terminal hydrolysis of N(alpha)-acylpeptides to release N(alpha)-acylated amino acids, was biochemically characterized using recombinant and native AAREs. A cDNA encoding a deduced Arabidopsis thaliana AARE (AtAARE) was cloned and sequenced. The deduced amino acid sequence encoded a 764 amino acid protein of 83.9 kDa, which was 31.8% identical with that of rat AARE. In particular, the proposed catalytic residues (Ser, Asp, and His) of AARE, called the "catalytic triad residues, " were completely conserved. Recombinant AtAARE was expressed in Escherichia coli and confirmed to be a functional AARE. Native AAREs were prepared from A. thaliana and cucumber (Cucumis sativus, L.) plants. Both native AAREs were tetrameric proteins of 350 kDa comprising four subunits of 82 kDa, and showed typical enzymological properties of other AAREs, i.e. sensitivity to diisopropyl fluorophosphate, an optimum pH of around 7.0, and an optimum temperature of 37 degrees C. Both the native and recombinant AAREs were immunochemically homologous. Intracelluar fractionation analysis showed that the AARE was mainly present in the stroma of chloroplasts. Native AARE degraded the glycated ribulose-1,5-bisphoshate carboxylase/oxygenase protein but not the native protein. Thus, plant AARE might be involved in not only catalysis of the N-terminal hydrolysis of N(alpha)-acylpeptides but also the elimination of glycated proteins.
ESTHER : Yamauchi_2003_J.Biochem_134_251
PubMedSearch : Yamauchi_2003_J.Biochem_134_251
PubMedID: 12966075
Gene_locus related to this paper: arath-AARE

Title : Cholesterol esterase accelerates intestinal cholesterol absorption - Ikeda_2002_Biochim.Biophys.Acta_1571_34
Author(s) : Ikeda I , Matsuoka R , Hamada T , Mitsui K , Imabayashi S , Uchino A , Sato M , Kuwano E , Itamura T , Yamada K , Tanaka K , Imaizumi K
Ref : Biochimica & Biophysica Acta , 1571 :34 , 2002
Abstract : Mechanisms of acceleration of cholesterol absorption by cholesterol esterase were investigated in various experimental conditions. Lymphatic recovery of cholesterol intubated as a micellar solution containing phosphatidylcholine (PC) into the duodenum was enhanced by the co-administration of cholesterol esterase in rats drained of bile and pancreatic juice. However, no accelerated incorporation was observed when cholesterol was solubilized in PC-depleted micelles. Cholesterol esterase dose-dependently accelerated the incorporation of cholesterol into differentiated Caco-2 cells, only when cholesterol was solubilized in PC-containing micelles. The accelerated incorporation of cholesterol into Caco-2 cells by cholesterol esterase disappeared when the enzyme was preincubated with a suicide inhibitor of cholesterol esterase. Cholesterol esterase has an activity as phospholipase A(2). When 10% of PC in bile salt micelles was replaced by lysophosphatidylcholine (lysoPC), the incorporation of cholesterol into Caco-2 cells was significantly accelerated. Cholesterol esterase enhanced the incorporation of micellar cholesterol into brush border membranes prepared from the rat jejunum. The addition of cholesterol esterase to bile salt micelles accelerated the release of micellar cholesterol in a dose-dependent manner, only when the micelles contained PC. These observations strongly suggest that cholesterol esterase hydrolyzes PC in bile salt micelles and thereby, accelerating the release of cholesterol from bile salt micelles. This may be a major cause of the acceleration of cholesterol absorption by cholesterol esterase.
ESTHER : Ikeda_2002_Biochim.Biophys.Acta_1571_34
PubMedSearch : Ikeda_2002_Biochim.Biophys.Acta_1571_34
PubMedID: 12031288

Title : A high molecular weight glutamyl endopeptidase and its endogenous inhibitors from cucumber leaves - Yamauchi_2001_J.Biochem_130_257
Author(s) : Yamauchi Y , Ejiri Y , Sugimoto T , Sueyoshi K , Oji Y , Tanaka K
Ref : J Biochem , 130 :257 , 2001
Abstract : We purified a glutamyl endopeptidase that is a major foliar endopeptidase in cucumber. The endopeptidase had a molecular mass of 400 kDa, consisted of four subunits of 97 kDa, and was inactivated by SH-modifying reagents. Its optimum pH and optimum temperature were 8.0 and 30-37 degrees C, respectively. An internal amino acid sequence of the endopeptidase was highly homologous to a partial sequence of unidentified proteins deduced from genetic information for Arabidopsis thaliana, soybean and rice, but not to the sequences of bacterial glutamyl endopeptidases or animal proteases. Therefore, the unidentified proteins might be glutamyl endopeptidases and be widely distributed only among plant species. The activity of the cucumber glutamyl endopeptidase was inhibited by at least three inhibitors existing in cucumber leaves. One of the inhibitors was a competitive inhibitor of 25 kDa, which did not significantly inhibit commercial endopeptidases derived from animals and microorganisms. This suggests that the cucumber glutamyl endopeptidase might be controlled by endogenous inhibitors in vivo.
ESTHER : Yamauchi_2001_J.Biochem_130_257
PubMedSearch : Yamauchi_2001_J.Biochem_130_257
PubMedID: 11481043
Gene_locus related to this paper: cucsa-a0a0a0k5t5

Title : Molecular basis of esterase D polymorphism in the pig - Omi_2000_Anim.Genet_31_413
Author(s) : Omi T , Tsuchida S , Onishi A , Amano T , Tanaka K , Iwamoto S , Kajii E
Ref : Anim Genet , 31 :413 , 2000
Abstract :
ESTHER : Omi_2000_Anim.Genet_31_413
PubMedSearch : Omi_2000_Anim.Genet_31_413
PubMedID: 11167536
Gene_locus related to this paper: pig-estd

Title : SDZ ENA 713 facilitates central cholinergic function and ameliorates spatial memory impairment in rats - Ohara_1997_Behav.Brain.Res_83_229
Author(s) : Ohara T , Tanaka K , Fukaya H , Demura N , Iimura A , Seno N
Ref : Behavioural Brain Research , 83 :229 , 1997
Abstract : We have clarified the effects of SDZ ENA 713 (ENA), a new phenyl-carbamate derivative, on the spatial learning impairment and neurochemical indices of central cholinergic neurons in rats. Basal forebrain (BF) lesioning with ibotenic acid markedly impaired acquisition ability in the water maze task without changing swimming rates and decreased choline acetyltransferase (ChAT) activity in the frontal cortex of rats. ENA (0.1, 0.2 mg/kg, p.o.) significantly ameliorated the impairment in acquisition ability in a dose-dependent manner. At 0.2 mg/kg, ENA prevented the reduction in ChAT activity. In normal rats, ENA (1 mg/kg, p.o.) increased extracellular ACh concentration of the prefrontal cortex. On the other hand, tissue concentrations of norepinephrine, serotonin, dopamine and their metabolites were not changed in the frontal cortex, hippocampus and striatum of normal rats. These results suggest that ENA ameliorates spatial learning disability by not only facilitating the cholinergic transmission, but normalizing impaired ChAT activity in the learning-impaired rat model.
ESTHER : Ohara_1997_Behav.Brain.Res_83_229
PubMedSearch : Ohara_1997_Behav.Brain.Res_83_229
PubMedID: 9062691

Title : Long-term time course of regional changes in cholinergic indices following transient ischemia in the spontaneously hypertensive rat brain - Ogawa_1996_Brain.Res_712_60
Author(s) : Ogawa N , Asanuma M , Tanaka K , Hirata H , Kondo Y , Goto M , Kawauchi M , Ogura T
Ref : Brain Research , 712 :60 , 1996
Abstract : Using an animal model of forebrain ischemia in spontaneously hypertensive rats (SHR) by 3-h bilateral carotid occlusion, and various indices of the cerebral cholinergic system were assessed for periods up to 24 weeks. The lesions observed histologically in the hippocampus of SHR 2 weeks after ischemia were less severe than those in the frontal cortex. Marked elevation of acetylcholine concentration was transiently observed in the frontal cortex, hippocampus and thalamus + midbrain at 2 weeks, and in the striatum at 1-4 weeks after ischemia. Choline acetyltransferase activity remained unchanged in all regions throughout the experimental period except for a minimal decrease in the frontal cortex at 4 weeks. Choline esterase (ChE) activity was slightly decreased in the frontal cortex at 2-4 weeks after ischemia but recovered by 8 weeks. A decrease in the hippocampus was seen at 8 weeks. The B(max) for the M1-receptor was significantly reduced by 2 weeks in the frontal cortex and by 4 weeks in the hippocampus. Low B(max) values in both regions persisted through week 24. These delayed hippocampal changes in the ChE activity and M1-receptor in SHR were similar to those of the very much delayed changes in M1-receptor previously reported in the gerbil model for transient ischemia. In contrast, Wistar-Kyoto rats (WKY), used as normotensive controls, exhibited no histological or biochemical changes for up to 24 weeks. The difference between SHR and WKY may depend on the more severe cerebral blood flow depletion during carotid ligation in the former. The chronic state of SHR after the transient ischemia may be a useful pathophysiological model for human cerebral infarctions with hypertension.
ESTHER : Ogawa_1996_Brain.Res_712_60
PubMedSearch : Ogawa_1996_Brain.Res_712_60
PubMedID: 8705308

Title : Sequence analysis of a 50 kb region between spo0H and rrnH on the Bacillus subtilis chromosome - Yasumoto_1996_Microbiology_142 ( Pt 11)_3039
Author(s) : Yasumoto K , Liu H , Jeong SM , Ohashi Y , Kakinuma S , Tanaka K , Kawamura F , Yoshikawa H , Takahashi H
Ref : Microbiology , 142 ( Pt 11) :3039 , 1996
Abstract : The 49630 bp spo0H-rrnH region of the Bacillus subtilis genome has been fully sequenced. The sequence contains one partial and 62 complete ORFs, one partial and three complete rRNA genes and a cluster of six tRNA genes. The direction of the transcription and translation of 61 ORFs is the same as that of the movement of the replication fork. A homology search of 40 ORFs in newly determined sequence revealed that 27 of them had significant similarity to known proteins such as elongation factor G, elongation factor Tu, pseudouridine synthase I and ribsosomal proteins. Two adjacent genes, ybaD and ybaE, appeared to encode proteins belonging to the ATP-binding cassette (ABC) family.
ESTHER : Yasumoto_1996_Microbiology_142 ( Pt 11)_3039
PubMedSearch : Yasumoto_1996_Microbiology_142 ( Pt 11)_3039
PubMedID: 8969501
Gene_locus related to this paper: bacsu-YBAC

Title : Report on 640 victims of the Tokyo subway sarin attack -
Author(s) : Okumura T , Takasu N , Ishimatsu S , Miyanoki S , Mitsuhashi A , Kumada K , Tanaka K , Hinohara S
Ref : Annals of Emergency Medicine , 28 :129 , 1996
PubMedID: 8759575

Title : Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus - Tanaka_1995_Neurochem.Res_20_663
Author(s) : Tanaka K , Mizukawa K , Ogawa N , Mori A
Ref : Neurochemical Research , 20 :663 , 1995
Abstract : We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.
ESTHER : Tanaka_1995_Neurochem.Res_20_663
PubMedSearch : Tanaka_1995_Neurochem.Res_20_663
PubMedID: 756636

Title : Chronic administration of acetylcholinesterase inhibitor in the senescent rat brain - Tanaka_1994_Neurobiol.Aging_15_721
Author(s) : Tanaka K , Ogawa N , Asanuma M , Kondo Y , Mori A
Ref : Neurobiology of Aging , 15 :721 , 1994
Abstract : The effects of chronic administration of ENA-713, an acetylcholinesterase (AChE) inhibitor, on pre- and postsynaptic cholinergic indices were examined in the senescent rat brain. In the senescent group, the acetylcholine (ACh) level was markedly reduced in the frontal cortex, hippocampus, striatum and thalamus+midbrain, but these reductions were completely prevented by ENA-713. Moreover, although choline acetyltransferase (ChAT) activity was also significantly decreased in these four regions, it recovered in the frontal cortex, hippocampus and thalamus+midbrain after ENA-713 treatment. In contrast, cholinesterase (ChE) activity was not changed in any experimental groups. The maximum number (Bmax) of muscarinic M1 receptor (M1-R) binding site in the frontal cortex in the senescent group was decreased without any change in affinity, but this decrease was also inhibited by ENA-713. Thus, these findings suggest that ENA-713 may have protective, neurotrophic and therapeutic effects on aging-induced cholinergic dysfunction and be useful for the treatment of aging-related dementia, such as the Alzheimer-type dementia.
ESTHER : Tanaka_1994_Neurobiol.Aging_15_721
PubMedSearch : Tanaka_1994_Neurobiol.Aging_15_721
PubMedID: 7891827

Title : Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia - Tanaka_1994_Neurochem.Res_19_117
Author(s) : Tanaka K , Ogawa N , Mizukawa K , Asanuma M , Kondo Y , Nishibayashi S , Mori A
Ref : Neurochem Res , 19 :117 , 1994
Abstract : The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.
ESTHER : Tanaka_1994_Neurochem.Res_19_117
PubMedSearch : Tanaka_1994_Neurochem.Res_19_117
PubMedID: 8183420

Title : Effects of the acetylcholinesterase inhibitor ENA-713 on ischemia-induced changes in acetylcholine and aromatic amine levels in the gerbil brain - Tanaka_1993_Arch.Int.Pharmacodyn.Ther_323_85
Author(s) : Tanaka K , Ogawa N , Asanuma M , Hirata H , Kondo Y , Nakayama N , Mori A
Ref : Archives Internationales de Pharmacodynamie et de Therapie , 323 :85 , 1993
Abstract : The effects of a new acetylcholinesterase inhibitor, ENA-713, on ischemia-induced changes in acetylcholine, monoamines, and their metabolites, were studied in the gerbil. ENA-713 (0.2 mg/kg) or saline was administered intraperitoneally to gerbils 30 min before induction of cerebral ischemia by bilateral carotid occlusion. Pretreatment with ENA-713 mitigated the ischemia-induced abnormalities of the cholinergic, dopaminergic and serotoninergic systems in the gerbil brain, although it had virtually no effect on acetylcholine, monoamines, or their metabolites in any region of the normal gerbil brain. These findings suggest that ENA-713 has beneficial effects against ischemia-induced cerebral disorders. Thus, ENA-713 seems to be promising as a preventive or therapeutic agent for cerebrovascular dementia due to cerebral ischemia and might be useful for the treatment of Alzheimer-type dementia which is associated with multiple neurotransmitter abnormalities in the brain.
ESTHER : Tanaka_1993_Arch.Int.Pharmacodyn.Ther_323_85
PubMedSearch : Tanaka_1993_Arch.Int.Pharmacodyn.Ther_323_85
PubMedID: 8250645

Title : Short-term changes in lipid and protein metabolism in liver transplants from living-related donors - Tanaka_1993_Am.J.Surg_166_32
Author(s) : Tanaka A , Sano K , Tanaka K , Honda K , Uemoto S , Takada Y , Yamaoka Y , Inamoto T , Shimahara Y , Mori K , et al.
Ref : American Journal of Surgery , 166 :32 , 1993
Abstract : The effects of liver transplantation involving living-related donors were investigated in 20 pediatric cases in terms of protein and lipid metabolism using the extent of cholesterol esterification and the levels of total cholesterol, lecithine-cholesterol acyltransferase, apolipoprotein A-I, cholinesterase, and rapid turnover proteins as parameters. Cholesterol esterification increased from preoperative values of 39% +/- 4% to 67% +/- 1% (mean +/- SEM, n = 17) at 3 weeks after liver transplantation in successful cases but decreased from the preoperative value of 45% +/- 10% to 26% +/- 6% (n = 3) at 3 weeks in unsuccessful cases. Cholinesterase, transferrin, and prealbumin levels remained low after 3 weeks even in successful cases. Patients who had partial liver transplantations from living-related donors showed rapid recovery of cholesterol esterification. However, patients with graft livers required an extensive period before normalization of protein metabolism occurred, indicating the necessity for long-term follow-up of recipient development.
ESTHER : Tanaka_1993_Am.J.Surg_166_32
PubMedSearch : Tanaka_1993_Am.J.Surg_166_32
PubMedID: 8101049

Title : [The histochemical study of the effects of estrogen on the forebrain cholinergic neurons of fetal female rats transplanted into the anterior eye chamber of adult female rats]. [Japanese] - Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
Author(s) : Tanaka K , Tamura T , Kawashima M , Ueda S , Matsumoto Y , Kawata M , Ogino Y , Yamamoto T , Honjo H , Okada H
Ref : Nippon Naibunpi Gakkai Zasshi Folia Endocrinologica Japonica , 69 :534 , 1993
Abstract : In order to clarify the effects of estrogen on cholinergic basal forebrain neurons, a cholinergic neuron in the diagonal band nucleus of the female fetal rat was implanted into the anterior eye chamber of the female adult rat. Some host rats were treated with 2mg estradiol valerate (E2v) injected every 3 days after ovariectomy while others were not 2 and 4 weeks after transplantation, the growth of cholinergic neurons in the graft was studied using acethylcholinesterase (AChE) histochemistry. At 2 weeks after transplantation, AChE positive neurons and fibers were densely distributed in the grafts of E2v treated rats. Also in grafts without E2v treatment, AChE positive neurons and fibers were found in all the grafts although their density was low. At 4 weeks, AChE staining was dense staining observed in both groups. These results indicate that neurotrophic effect of estrogen on the cholinergic basal forebrain neurons.
ESTHER : Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
PubMedSearch : Tanaka_1993_Nihon.Naibunpi.Gakkai.Zasshi_69_534
PubMedID: 8330655

Title : Effects of substitution of putative transmembrane segments on nicotinic acetylcholine receptor function - Tobimatsu_1987_FEBS.Lett_222_56
Author(s) : Tobimatsu T , Fujita Y , Fukuda K , Tanaka K , Mori Y , Konno T , Mishina M , Numa S
Ref : FEBS Letters , 222 :56 , 1987
Abstract : Mutants of the Torpedo nicotinic acetylcholine receptor in which each of the putative transmembrane segments of the alpha-subunit is replaced by the hydrophobic transmembrane segment of the vesicular stomatitis virus glycoprotein or of the human interleukin-2 receptor have been produced in Xenopus oocytes by cDNA manipulations. Functional analysis of these mutants shows that the hydrophobic segment M4 can be replaced by foreign transmembrane sequences without loss of channel activity. It is also suggested that the hydrophobic segments M1, M2 and M3 and the amphipathic segment MA are important for efficient expression of the acetylcholine receptor on the cell surface and that the specific amino acid sequence of segment M2 may be involved in channel activity.
ESTHER : Tobimatsu_1987_FEBS.Lett_222_56
PubMedSearch : Tobimatsu_1987_FEBS.Lett_222_56
PubMedID: 3653401

Title : Functional properties of nicotinic acetylcholine receptor subunits expressed in various combinations - Kurosaki_1987_FEBS.Lett_214_253
Author(s) : Kurosaki T , Fukuda K , Konno T , Mori Y , Tanaka K , Mishina M , Numa S
Ref : FEBS Letters , 214 :253 , 1987
Abstract : The four kinds of subunits of the Torpedo californica nicotinic acetylcholine receptor have been produced in various combinations by injecting Xenopus oocytes with the corresponding subunit-specific mRNAs synthesized by transcription in vitro of the cloned cDNAs. Functional analysis suggests that association of the alpha-subunit with either the gamma- or the delta-subunit is a prerequisite for generating the conformation necessary for agonist binding. The acetylcholine receptor devoid of either the beta-, gamma- or delta-subunit exhibits weak channel activity.
ESTHER : Kurosaki_1987_FEBS.Lett_214_253
PubMedSearch : Kurosaki_1987_FEBS.Lett_214_253
PubMedID: 2436944

Title : Primary structure of beta subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence - Tanabe_1984_Eur.J.Biochem_144_11
Author(s) : Tanabe T , Noda M , Furutani Y , Takai T , Takahashi H , Tanaka K , Hirose T , Inayama S , Numa S
Ref : European Journal of Biochemistry , 144 :11 , 1984
Abstract : Clones harbouring cDNA sequences for the beta subunit precursor of the acetylcholine receptor from calf skeletal muscle have been isolated. Nucleotide sequence analysis of the cloned cDNA has disclosed the primary structure of this polypeptide, which consists of 505 amino acids including a hydrophobic prepeptide of 24 amino acids. The beta subunit of the calf muscle acetylcholine receptor, like the alpha and gamma subunits of the same receptor and the alpha subunit of its human counterpart, exhibits structural features common to all four subunits of the Torpedo electroplax receptor, apparently being oriented across the membrane in the same manner as proposed for the fish receptor subunits. The degree of sequence homology between the calf and Torpedo beta subunits (59%) is comparable to that between the gamma subunits (56%), but is lower than that between the alpha subunits of the two species (81%). Some regions of the beta subunit molecule, including the region corresponding to the putative acetylcholine binding area on the alpha subunit and the region encompassing the clustered putative transmembrane segments M1, M2 and M3, are relatively well conserved between the two species.
ESTHER : Tanabe_1984_Eur.J.Biochem_144_11
PubMedSearch : Tanabe_1984_Eur.J.Biochem_144_11
PubMedID: 6548186