Ito Y

References (30)

Title : Organophosphate agent action at the fatty acid amide hydrolase enhancing anandamide-induced apoptosis in NG108-15 cells - Terajima_2023_J.Toxicol.Sci_48_421
Author(s) : Terajima T , Inoue H , Shimomura K , Iwasaki F , Sasaki A , Ito Y , Kamijima M , Tomizawa M
Ref : Journal of Toxicological Sciences , 48 :421 , 2023
Abstract : Organophosphate (OP) agents are continuously utilized in large amount throughout the globe for crop protection and public health, thereby creating a potential concern on human health. OP agent as an anticholinesterase also acts on the endocannabinoid (EC)-hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), to reveal unexpected adverse effects including ADHD-like behaviors in adolescent male rats. The present investigation examines a hypothesis that OP compound inhibiting the EC-hydrolase(s) dysregulates the EC-signaling system, triggering apoptosis in neuronal cells. Ethyl octylphosphonofluoridate (EOPF), as an OP probe, preferably acts on FAAH over MAGL in intact NG108-15 cells. Anandamide (AEA), an endogenous FAAH substrate, is cytotoxic in a concentration-dependent manner, although 2-arachidonoylglycerol, an endogenous MAGL substrate, gives no effect in the concentrations examined here. EOPF pretreatment markedly enhances AEA-induced cytotoxicity. Interestingly, the cannabinoid receptor blocker AM251 diminishes AEA-induced cell death, whereas AM251 does not prevent the cell death in the presence of EOPF. The consistent results are displayed in apoptosis markers evaluation (caspases and mitochondrial membrane potential). Accordingly, FAAH inhibition by EOPF suppresses AEA-metabolism, and accumulated excess AEA overstimulates both the cannabinoid receptor- and mitochondria-mediated apoptotic pathways.
ESTHER : Terajima_2023_J.Toxicol.Sci_48_421
PubMedSearch : Terajima_2023_J.Toxicol.Sci_48_421
PubMedID: 37394655

Title : Residue levels of organophosphate pesticides and dialkylphosphates in agricultural products in Japan - Tsuchiyama_2023_Environ.Res__116518
Author(s) : Tsuchiyama T , Ito Y , Taniguchi M , Katsuhara M , Miyazaki H , Kamijima M
Ref : Environ Research , :116518 , 2023
Abstract : High urinary levels of dialkylphosphates (DAPs), which are common structures of organophosphate pesticides (OPs), have been associated with several adverse health outcomes in human biomonitoring studies. Previous studies have indicated that dietary OP exposure and ingestion of environmentally degraded DAP, which is inactive with acetylcholinesterase, can lead to an increase in urinary DAP levels in the general population. However, the specific food sources contributing to the intake of OPs and DAPs have not been identified. In this study, we analyzed the levels of OPs and preformed DAPs in various food items. DAP levels were markedly high in certain fruits, such as persimmon, apple juice, kiwi, and mandarin. In contrast, only moderate levels of OPs were detected in these foods. Furthermore, the levels of OPs and DAPs were positively associated with vegetables, whereas no such association was observed in fruits. Increased consumption of certain fruits presumably leads to a marked increase in urinary DAP levels in individuals despite limited exposure to OPs, resulting in reduced reliability of urinary DAPs as a marker of OP exposure. Therefore, the possible effects of dietary habits and the resulting intake of preformed DAPs should be considered when interpreting biomonitoring data of urinary DAPs. Additionally, DAP levels in most organic foods were much lower than those in conventional foods, suggesting that the reduction in urinary DAPs by organic diet intervention may be mainly attributed to the reduced intake of preformed DAPs rather than reduced exposure to OPs. Therefore, urinary DAP levels may not be suitable indicators for evaluating ingested OP exposure.
ESTHER : Tsuchiyama_2023_Environ.Res__116518
PubMedSearch : Tsuchiyama_2023_Environ.Res__116518
PubMedID: 37394165

Title : Assessment of drug-drug interaction and optimization in capecitabine and irinotecan combination regimen using a physiologically based pharmacokinetic model - Sakai_2021_J.Pharm.Sci__
Author(s) : Sakai S , Kobuchi S , Ito Y , Sakaeda T
Ref : J Pharm Sci , : , 2021
Abstract : Capecitabine and irinotecan (CPT-11) combination regimen (XELIRI) is used for colorectal cancer treatment. Capecitabine is metabolized to 5-fluorouracil (5-FU) by three enzymes, including carboxylesterase (CES). CES can also convert CPT-11 to 7-ethyl-10-hydroxycamptotecin (SN-38). CES is involved in the metabolic activation of both capecitabine and CPT-11, and it is possible that drug-drug interactions occur in XELIRI. Here, a physiologically based pharmacokinetic (PBPK) model was developed to evaluate drug-drug interactions. Capecitabine (180 mg/kg) and CPT-11 (180 mg/m(2)) were administered to rats, and blood (250 microL) was collected from the jugular vein nine times after administration. Metabolic enzyme activities and K(i) values were calculated through in vitro experiments. The plasma concentration of 5-FU in XELIRI was significantly decreased compared to capecitabine monotherapy, and metabolism of capecitabine by CES was inhibited by CPT-11. A PBPK model was developed based on the in vivo and in vitro results. Furthermore, a PBPK model-based simulation was performed with the capecitabin dose ranging from 0 to 1000mol/kg in XELIRI, and it was found that an approximately 1.7-fold dosage of capecitabine was required in XELIRI for comparable 5-FU exposure with capecitabine monotherapy. PBPK model-based simulation will contribute to the optimization of colorectal cancer chemotherapy using XELIRI.
ESTHER : Sakai_2021_J.Pharm.Sci__
PubMedSearch : Sakai_2021_J.Pharm.Sci__
PubMedID: 34965386

Title : Non-linear model analysis of the relationship between cholinesterase activity in rats exposed to 2, 2-dichlorovinyl dimethylphosphate (dichlorvos) and its metabolite concentrations in urine - Sato_2021_Toxicology__152679
Author(s) : Sato H , Ito Y , Hanai C , Nishimura M , Ueyama J , Kamijima M
Ref : Toxicology , :152679 , 2021
Abstract : Urinary dialkylphosphates (DAPs) are measured to assess exposure to organophosphorus pesticides (OPs), but they are common metabolites of OPs and not specific indices for individual agents. Biomonitoring (BM) of urinary DAPs has been widely adopted as an assessment of individual exposure in general environments, however, guidance values for DAPs based on health effects have yet to be established. The present study aimed to clarify the relationship between the amount of urinary dimethylphosphate (DMP), a metabolite of dichlorvos (DDVP), and the inhibition of cholinesterase (ChE) activity in rats exposed to DDVP. The relationship was analyzed using a nonlinear model analysis, and the excretion level of urinary DMP equivalent to ChE 20% inhibition (EL20) and the lower limit of the 95% confidence interval of EL20 (ELL20) were estimated. EL20 and ELL20 (mg/24 h urine) of brain, erythrocyte, and plasma ChE activities after 10-day administration of DDVP were 0.21 and 0.15, 0.11 and 0.06, and 0.23 and 0.09, respectively. Extrapolating ELL20 of the brain ChE to humans, the range of 24 h urinary DMP concentration according to the 20% inhibition of cholinesterase activity was estimated to be 20.5-30.8 mg/l. In conclusion, the amount of urinary DMP as ELL20 for DDVP exposure was identified and could probably be used as a novel index for the assessment of risk from OP exposure. Further studies are needed to clarify the ELL20 s derived from OPs other than DDVP, for informing efforts to establish guidance values of urinary OP metabolites that should prevent neurotoxicity.
ESTHER : Sato_2021_Toxicology__152679
PubMedSearch : Sato_2021_Toxicology__152679
PubMedID: 33460720

Title : Assessment of pharmacokinetic variations of capecitabine after multiple administration in rats: a physiologically based pharmacokinetic model - Sakai_2020_Cancer.Chemother.Pharmacol__
Author(s) : Sakai S , Kobuchi S , Ito Y , Sakaeda T
Ref : Cancer Chemother Pharmacol , : , 2020
Abstract : PURPOSE: Capecitabine is a prodrug of 5-fluorouracil (5-FU) used for the treatment of colorectal cancer, with a two-week course of administration. However, the variance in plasma concentration and metabolic enzyme activities after multiple administration of capecitabine and its metabolites is unknown. The aim of this study was to identify the variance and predict the plasma concentration profile of capecitabine and its metabolites, using metabolic enzyme activities, to develop a more effective and safer medication. METHODS: Rats orally received 180 mg/kg of capecitabine once a day for two weeks. Blood samples were collected nine times, and plasma concentration was measured on day 1, 7, and 14. The liver and small intestine were removed after blood sampling and were used in vitro to evaluate metabolic enzyme activities of carboxylesterase, cytidine deaminase, and thymidine phosphorylase. A physiologically based pharmacokinetic (PBPK) model was developed using in vitro results. RESULTS: Area under the plasma concentration-time curve from 0 h to infinity of 5-FU on day 7 and day 14 was significantly lower than that on day 1. Intrinsic clearance of thymidine phosphorylase in the liver on day 7 and day 14 was 1.4 and 1.3 times lower than that on day 1, respectively. The PBPK model described the observed plasma concentration of capecitabine and its metabolites. CONCLUSION: The decreased plasma concentration of capecitabine was caused by decreased metabolic enzyme activity. Efficacy can be improved by dose adjustment of capecitabine based on metabolic enzyme activities, using the PBPK model.
ESTHER : Sakai_2020_Cancer.Chemother.Pharmacol__
PubMedSearch : Sakai_2020_Cancer.Chemother.Pharmacol__
PubMedID: 32240335

Title : Soluble epoxide hydrolase in podocytes is a significant contributor to renal function under hyperglycemia - Bettaieb_2017_Biochim.Biophys.Acta_1861_2758
Author(s) : Bettaieb A , Koike S , Hsu MF , Ito Y , Chahed S , Bachaalany S , Gruzdev A , Calvo-Rubio M , Lee KSS , Inceoglu B , Imig JD , Villalba JM , Zeldin DC , Hammock BD , Haj FG
Ref : Biochimica & Biophysica Acta , 1861 :2758 , 2017
Abstract : BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal function. The aim of this study is to investigate the contribution of sEH in podocytes to hyperglycemia-induced renal injury. MATERIALS AND
METHODS: Mice with podocyte-specific sEH disruption (pod-sEHKO) were generated, and alterations in kidney function were determined under normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia.
RESULTS: sEH protein expression increased in murine kidneys under HFD- and STZ-induced hyperglycemia. sEH deficiency in podocytes preserved renal function and glucose control and mitigated hyperglycemia-induced renal injury. Also, podocyte sEH deficiency was associated with attenuated hyperglycemia-induced renal endoplasmic reticulum (ER) stress, inflammation and fibrosis, and enhanced autophagy. Moreover, these effects were recapitulated in immortalized murine podocytes treated with a selective sEH pharmacological inhibitor. Furthermore, pharmacological-induced elevation of ER stress or attenuation of autophagy in immortalized podocytes mitigated the protective effects of sEH inhibition.
CONCLUSIONS: These findings establish sEH in podocytes as a significant contributor to renal function under hyperglycemia. GENERAL SIGNIFICANCE: These data suggest that sEH is a potential therapeutic target for podocytopathies.
ESTHER : Bettaieb_2017_Biochim.Biophys.Acta_1861_2758
PubMedSearch : Bettaieb_2017_Biochim.Biophys.Acta_1861_2758
PubMedID: 28757338

Title : The role of plasma lipoprotein lipase, hepatic lipase and GPIHBP1 in the metabolism of remnant lipoproteins and small dense LDL in patients with coronary artery disease - Muraba_2017_Clin.Chim.Acta_476_146
Author(s) : Muraba Y , Koga T , Shimomura Y , Ito Y , Hirao Y , Kobayashi J , Kimura T , Nakajima K , Murakami M
Ref : Clinica Chimica Acta , 476 :146 , 2017
Abstract : BACKGROUND: The relationship between plasma lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), glycosylphosphatidylinositol anchored HDL binding protein1 (GPIHBP1) concentration and the metabolism of remnant lipoproteins (RLP) and small dense LDL (sdLDL) in patients with coronary artery disease (CAD) is not fully elucidated. METHODS: One hundred patients who underwent coronary angiography were enrolled. The plasma LPL, HTGL and GPIHBP1 concentrations were determined by ELISA. The time dependent changes in those lipases, lipids and lipoproteins were studied at a time-point just before, and 15min, 4h and 24h after heparin administration. RESULTS: The LPL concentration exhibited a significant positive correlation with HDL-C, and inversely correlated with TG and RLP-C. The HTGL concentration was positively correlated with RLP-C and sdLDL-C. The HTGL ratio of the pre-heparin/post-heparin plasma concentration and sdLDL-C/LDL-C ratio were significantly greater in CAD patients than in non-CAD patients. GPIHBP1 was positively correlated with LPL and inversely correlated with RLP-C and sdLDL-C. CONCLUSION: The HTGL concentration was positively correlated with RLP-C and sdLDL-C, while LPL and GPIHBP1 were inversely correlated with RLP-C and sdLDL-C. These results suggest that elevated HTGL is associated with increased CAD risk, while elevated LPL is associated with a reduction of CAD risk.
ESTHER : Muraba_2017_Clin.Chim.Acta_476_146
PubMedSearch : Muraba_2017_Clin.Chim.Acta_476_146
PubMedID: 29174344
Gene_locus related to this paper: human-LIPC , human-LPL

Title : Evaluation of the impact of RNA preservation methods of spiders for de novo transcriptome assembly - Kono_2016_Mol.Ecol.Resour_16_662
Author(s) : Kono N , Nakamura H , Ito Y , Tomita M , Arakawa K
Ref : Mol Ecol Resour , 16 :662 , 2016
Abstract : With advances in high-throughput sequencing technologies, de novo transcriptome sequencing and assembly has become a cost-effective method to obtain comprehensive genetic information of a species of interest, especially in nonmodel species with large genomes such as spiders. However, high-quality RNA is essential for successful sequencing, and sample preservation conditions require careful consideration for the effective storage of field-collected samples. To this end, we report a streamlined feasibility study of various storage conditions and their effects on de novo transcriptome assembly results. The storage parameters considered include temperatures ranging from room temperature to -80 degrees C; preservatives, including ethanol, RNAlater, TRIzol and RNAlater-ICE; and sample submersion states. As a result, intact RNA was extracted and assembly was successful when samples were preserved at low temperatures regardless of the type of preservative used. The assemblies as well as the gene expression profiles were shown to be robust to RNA degradation, when 30 million 150-bp paired-end reads are obtained. The parameters for sample storage, RNA extraction, library preparation, sequencing and in silico assembly considered in this work provide a guideline for the study of field-collected samples of spiders.
ESTHER : Kono_2016_Mol.Ecol.Resour_16_662
PubMedSearch : Kono_2016_Mol.Ecol.Resour_16_662
PubMedID: 26561354
Gene_locus related to this paper: partp-a0a2l2yf54 , partp-a0a2l2y331 , partp-a0a2l2y9v9 , partp-a0a2l2ya50

Title : Genome evolution in the allotetraploid frog Xenopus laevis - Session_2016_Nature_538_336
Author(s) : Session AM , Uno Y , Kwon T , Chapman JA , Toyoda A , Takahashi S , Fukui A , Hikosaka A , Suzuki A , Kondo M , van Heeringen SJ , Quigley I , Heinz S , Ogino H , Ochi H , Hellsten U , Lyons JB , Simakov O , Putnam N , Stites J , Kuroki Y , Tanaka T , Michiue T , Watanabe M , Bogdanovic O , Lister R , Georgiou G , Paranjpe SS , van Kruijsbergen I , Shu S , Carlson J , Kinoshita T , Ohta Y , Mawaribuchi S , Jenkins J , Grimwood J , Schmutz J , Mitros T , Mozaffari SV , Suzuki Y , Haramoto Y , Yamamoto TS , Takagi C , Heald R , Miller K , Haudenschild C , Kitzman J , Nakayama T , Izutsu Y , Robert J , Fortriede J , Burns K , Lotay V , Karimi K , Yasuoka Y , Dichmann DS , Flajnik MF , Houston DW , Shendure J , DuPasquier L , Vize PD , Zorn AM , Ito M , Marcotte EM , Wallingford JB , Ito Y , Asashima M , Ueno N , Matsuda Y , Veenstra GJ , Fujiyama A , Harland RM , Taira M , Rokhsar DS
Ref : Nature , 538 :336 , 2016
Abstract : To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.
ESTHER : Session_2016_Nature_538_336
PubMedSearch : Session_2016_Nature_538_336
PubMedID: 27762356
Gene_locus related to this paper: xenla-a0a1l8f4t7 , xenla-a0a1l8fbc6 , xenla-a0a1l8fct2 , xenla-q2tap9 , xenla-q4klb6 , xenla-q5xh09 , xenla-q6ax59 , xenla-q6dcw6 , xenla-q6irp4 , xenla-q6pad5 , xenla-q7sz70 , xenla-Q7ZXQ6 , xenla-q66kx1 , xenla-q640y7 , xenla-q642r3 , xenla-Q860X9 , xenla-BCHE2 , xenla-a0a1l8g7v4 , xenla-a0a1l8g1u7 , xenla-a0a1l8fmc5 , xenla-a0a1l8g467 , xenla-a0a1l8g4e4 , xenla-a0a1l8ga66 , xenla-a0a1l8gaw4 , xenla-a0a1l8gt68 , xenla-a0a1l8h0b2 , xenla-a0a1l8fdr1 , xenla-a0a1l8fdt7 , xenla-a0a1l8fi72 , xenla-a0a1l8fi73 , xenla-a0a1l8fi77 , xenla-a0a1l8fi96 , xenla-a0a1l8hc38 , xenla-a0a1l8hn27 , xenla-a0a1l8hry6 , xenla-a0a1l8hw96 , xenla-a0a1l8i2x6 , xenla-a0a1l8hei7 , xenla-a0a1l8gnd1 , xenla-a0a1l8i2g3 , xenla-a0a1l8hdn0 , xenla-a0a1l8h622

Title : Lipase member H frequently overexpressed in human esophageal adenocarcinomas - Ishimine_2016_Tumour.Biol_37_2075
Author(s) : Ishimine H , Zhou R , Sumitomo K , Ito Y , Seki Y , Yoshida Y , Kurisaki A
Ref : Tumour Biol , 37 :2075 , 2016
Abstract : Esophageal cancer is one of the most frequent causes of cancer-related deaths worldwide. This is due to its asymptomatic nature or mild nonspecific symptoms. Most patients are diagnosed after appearance of prominent symptoms, and tumors are frequently accompanied by severe infiltration. Therefore, molecular biomarkers for the prognosis of early-stage esophageal cancer are desired. In this study, we examined the prognostic potential of lipase H (LIPH), a recently reported biomarker for lung adenocarcinoma and squamous carcinoma. We found that LIPH mRNA is also frequently upregulated in esophageal adenocarcinoma. Immunohistochemical analysis confirmed LIPH protein expression in various esophageal tumor tissue sections. Interestingly, higher expression of LIPH in esophageal adenocarcinoma showed a positive correlation with longer survival of patients. Our data suggest that LIPH may have prognostic value for esophageal cancer.
ESTHER : Ishimine_2016_Tumour.Biol_37_2075
PubMedSearch : Ishimine_2016_Tumour.Biol_37_2075
PubMedID: 26341494

Title : Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers - Ito_2014_Environ.Health.Prev.Med_19_117
Author(s) : Ito Y , Kamijima M , Hasegawa C , Tagawa M , Kawai T , Miyake M , Hayashi Y , Naito H , Nakajima T
Ref : Environ Health Prev Med , 19 :117 , 2014
Abstract : OBJECTIVES: This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. METHODS: The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. RESULTS: Microsomal lipase activity was significantly lower in humans than in mice. The V max/K m value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. CONCLUSION: The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.
ESTHER : Ito_2014_Environ.Health.Prev.Med_19_117
PubMedSearch : Ito_2014_Environ.Health.Prev.Med_19_117
PubMedID: 24078404

Title : Indiplon is hydrolyzed by arylacetamide deacetylase in human liver - Shimizu_2014_Drug.Metab.Dispos_42_751
Author(s) : Shimizu M , Fukami T , Ito Y , Kurokawa T , Kariya M , Nakajima M , Yokoi T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :751 , 2014
Abstract : Human arylacetamide deacetylase (AADAC) catalyzes the hydrolysis of some clinically used drugs, but the information available on its substrates is limited. To increase our knowledge of the AADAC substrates, we examined whether AADAC catalyzes the hydrolysis of indiplon, which was initially developed as a hypnotic sedative drug. It has been reported that approximately 30-40% of the administered indiplon was hydrolyzed to deacetylindiplon in humans, but the enzyme responsible for this hydrolysis had not been identified. We detected high levels of indiplon hydrolase activity in human liver microsomes (HLMs), but the levels found in human liver cytosol and plasma were scarcely detectable. Recombinant AADAC showed a high level of indiplon hydrolase activity, whereas recombinant carboxylesterase 1 (CES1) and 2 (CES2) showed marginal activity. The indiplon hydrolase activity of HLM was potently inhibited by vinblastine, a potent inhibitor of AADAC and CES2, but it was not inhibited by digitonin and telmisartan, inhibitors of CES1 and CES2, respectively. In a panel of 24 individual HLM samples, the indiplon hydrolase activities were significantly correlated with the hydrolase activities of flutamide, phenacetin, and rifampicin, which are known AADAC substrates. An HLM sample with a homozygous AADAC*3 allele, which was previously found to exhibit decreased enzyme activity, showed the lowest indiplon hydrolase activity among the 24 tested samples. Collectively, we found that human AADAC is responsible for the hydrolysis of indiplon. Thus, we can add indiplon to the list of human AADAC substrates.
ESTHER : Shimizu_2014_Drug.Metab.Dispos_42_751
PubMedSearch : Shimizu_2014_Drug.Metab.Dispos_42_751
PubMedID: 24464802

Title : Organophosphate agents induce plasma hypertriglyceridemia in mouse via single or dual inhibition of the endocannabinoid hydrolyzing enzyme(s) - Suzuki_2014_Toxicol.Lett_225_153
Author(s) : Suzuki H , Ito Y , Noro Y , Koketsu M , Kamijima M , Tomizawa M
Ref : Toxicol Lett , 225 :153 , 2014
Abstract : Diverse serine hydrolases including endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been suggested as secondary targets for organophosphate (OP) agents to exert adverse toxic effects such as lipid homeostasis disruption. The goal of this investigation is to verify that a major OP insecticide fenitrothion (FNT) induces plasma hypertriglyceridemia through the inhibition of FAAH and/or MAGL in comparison with that elicited by isopropyl dodecylfluorophosphonate (IDFP), a potent FAAH/MAGL inhibitor. Fasted mice were treated intraperitoneally with FNT or IDFP and were subsequently sacrificed for evaluations of plasma triglyceride (TG) levels and liver FAAH/MAGL activities. Plasma TG levels were significantly enhanced by the FNT or IDFP treatment (1.7- or 4.8-fold, respectively) compared with that of vehicle control. The IDFP exposure reduced the liver FAAH and MAGL activities, whereas the FNT exposure led to the preferential FAAH inhibition. The brain acetylcholinesterase was almost unaffected by the FNT or IDFP treatment, thus leading to no neurotoxic sign. Intriguingly, the TG elevations were averted by concomitant administration with the cannabinoid receptor antagonist AM251. The present findings suggest that OP agents induce plasma hypertriglyceridemia in mouse through single or dual inhibition of FAAH or/and MAGL, apparently leading to overstimulation of cannabinoid signal regulating energy metabolism.
ESTHER : Suzuki_2014_Toxicol.Lett_225_153
PubMedSearch : Suzuki_2014_Toxicol.Lett_225_153
PubMedID: 24361246

Title : An Orphan Esterase ABHD10 Modulates Probenecid Acyl Glucuronidation in Human Liver - Ito_2014_Drug.Metab.Dispos_42_2109
Author(s) : Ito Y , Fukami T , Yokoi T , Nakajima M
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :2109 , 2014
Abstract : Probenecid, a widely used uricosuric agent, is mainly metabolized to probenecid acyl glucuronide (PRAG), which is considered a causal substance of severe allergic or anaphylactoid reactions. PRAG can be hydrolyzed (deglucuronidated) to probenecid. The purpose of this study was to identify enzymes responsible for probenecid acyl glucuronidation and PRAG deglucuronidation in human livers and to examine the effect of deglucuronidation in PRAG formation. In human liver homogenates (HLHs), the intrinsic clearance (CLint) of PRAG deglucuronidation was much greater (497-fold) than that of probenecid acyl glucuronidation. Evaluation of PRAG formation by recombinant UDP-glucuronosyltransferase (UGT) isoforms and an inhibition study using HLHs as an enzyme source demonstrated that multiple UGT isoforms, including UGT1A1, UGT1A9, and UGT2B7, catalyzed probenecid acyl glucuronidation. We found that recombinant alpha/beta hydrolase domain containing 10 (ABHD10) substantially catalyzed PRAG deglucuronidation activity, whereas carboxylesterases did not. Similar inhibitory patterns by chemicals between HLHs and recombinant ABHD10 supported the major contribution of ABHD10 to PRAG deglucuronidation in human liver. Interestingly, it was demonstrated that the CLint value of probenecid acyl glucuronidation in HLHs was increased by 1.7-fold in the presence of phenylmethylsulfonyl fluoride, which potently inhibited ABHD10 activity. In conclusion, we found that PRAG deglucuronidation catalyzed by ABHD10 suppressively regulates PRAG formation via multiple UGT enzymes in human liver. The balance of activities by these enzymes is important for the formation of PRAG, which may be associated with the adverse reactions observed after probenecid administration.
ESTHER : Ito_2014_Drug.Metab.Dispos_42_2109
PubMedSearch : Ito_2014_Drug.Metab.Dispos_42_2109
PubMedID: 25217485
Gene_locus related to this paper: human-ABHD10 , mouse-abhda

Title : Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas - Seki_2014_Biochem.Biophys.Res.Commun_443_1141
Author(s) : Seki Y , Yoshida Y , Ishimine H , Shinozaki-Ushiku A , Ito Y , Sumitomo K , Nakajima J , Fukayama M , Michiue T , Asashima M , Kurisaki A
Ref : Biochemical & Biophysical Research Communications , 443 :1141 , 2014
Abstract : Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.
ESTHER : Seki_2014_Biochem.Biophys.Res.Commun_443_1141
PubMedSearch : Seki_2014_Biochem.Biophys.Res.Commun_443_1141
PubMedID: 24380866
Gene_locus related to this paper: human-LIPH

Title : Molecular Cloning and Transcript Expression of Genes Encoding Two Types of Lipoprotein Lipase in the Ovary of Cutthroat Trout, Oncorhynchus clarki - Ryu_2013_Zoolog.Sci_30_224
Author(s) : Ryu YW , Tanaka R , Kasahara A , Ito Y , Hiramatsu N , Todo T , Sullivan CV , Hara A
Ref : Zoolog Sci , 30 :224 , 2013
Abstract : Large amounts of neutral lipids (NLs) are stored as lipid droplets in the ooplasm of fish oocytes, providing an essential energy resource for developing embryos and larvae. However, little is known about the origin of such lipids or about mechanisms underlying their uptake and accumulation in oocytes. We have proposed a model for this lipidation of teleost oocytes, as follows: very low density lipoprotein (Vldl) is metabolized by lipoprotein lipase (Lpl) outside and/or inside of the oocyte and the resulting fatty acids (FAs) are then utilized for de novo biosynthesis of NLs. As a first step toward verification of this model, cDNAs for genes encoding two types of Lpl, lpl and lpl2, were cloned from the ovary of cutthroat trout, Oncorhynchus clarki. Examination of Lpl polypeptide sequences deduced from the cDNAs revealed features similar to LPLs/Lpls in other species, including several conserved structural and functional domains. Both types of lpl mRNA were highly expressed in lipid storage tissues (e.g., adipose tissue, muscle, and ovary) and were predominantly expressed in the granulosa cells of ovarian follicles. Ovarian lpl1 mRNA levels showed a remarkable peak in April (early oocyte lipid droplet stage) and then decreased to low values sustained until November (mid-vitellogenesis), after which time a small peak in lpl1 gene expression was observed in December (late vitellogenesis). The mRNA levels of lpl2 also were elevated in April and were highest in June (late lipid droplet stage), but did not show other pronounced changes. These results suggest that, in the cutthroat trout, Vldl is metabolized by the action of Lpls in the granulosa cell layer to generate free FAs for uptake and biosynthesis of neutral lipids by growing oocytes.
ESTHER : Ryu_2013_Zoolog.Sci_30_224
PubMedSearch : Ryu_2013_Zoolog.Sci_30_224
PubMedID: 23480383
Gene_locus related to this paper: oncmy-a0a060vy20 , oncmy-a0a060y788

Title : Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice - Wang_2012_Reprod.Toxicol_34_489
Author(s) : Wang D , Kamijima M , Okamura A , Ito Y , Yanagiba Y , Jia XF , Naito H , Ueyama J , Nakajima T
Ref : Reprod Toxicol , 34 :489 , 2012
Abstract : The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 mumol/kg/day) or cis-permethrin (90 mumol/kg/day) alone or in combination (100 mumol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.
ESTHER : Wang_2012_Reprod.Toxicol_34_489
PubMedSearch : Wang_2012_Reprod.Toxicol_34_489
PubMedID: 22944209

Title : New analytical method for sensitive quantification of urinary 3-methyl-4-nitrophenol to assess fenitrothion exposure in general population and occupational sprayers - Okamura_2012_Toxicol.Lett_210_220
Author(s) : Okamura A , Saito I , Ueyama J , Ito Y , Nakajima T , Kamijima M
Ref : Toxicol Lett , 210 :220 , 2012
Abstract : The measurement of blood cholinesterase (ChE) activities is adopted worldwide for biological monitoring of exposure to organophosphorus insecticides (OPs). Recent development of analytical chemistry has made sensitive quantification possible of non-specific OP metabolites, dialkylphosphates, in urine as a biomarker of low-level OP exposure. In this study, we established a method for quantification of urinary 3-methyl-4-nitrophenol (MNP), a specific metabolite of fenitrothion (FNT), and a parathion metabolite p-nitrophenol (PNP), using gas chromatography-mass spectrometry. The limits of detection of MNP and PNP were 0.3 and 0.5mug/L, respectively. The method enabled the quantification of both free and conjugated metabolites. This method was actually applied to monitor human urine in summer and winter in FNT sprayers (N=29 and 9, respectively) and control workers (N=17 and 29, respectively). Geometric mean total MNP concentrations (mug/gcreatinine) in the FNT sprayers (28.8 in summer and 8.6 in winter) were significantly higher than those of the controls (3.1 in summer and 2.3 in winter) in both seasons. Among the sprayers, total MNP concentrations in summer were significantly higher than in winter. In contrast, no significant difference in total PNP concentrations was observed between FNT sprayers (geometric mean 3.4 in summer and 3.0 in winter) and controls (3.6 in summer and 2.1 in winter). No seasonal difference was observed in each group. In conclusion, the present new method is sensitive enough for biological monitoring of FNT and parathion metabolites even in a non-spraying population.
ESTHER : Okamura_2012_Toxicol.Lett_210_220
PubMedSearch : Okamura_2012_Toxicol.Lett_210_220
PubMedID: 22027349

Title : Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice - Shirakawa_2011_Diabetes_60_1246
Author(s) : Shirakawa J , Fujii H , Ohnuma K , Sato K , Ito Y , Kaji M , Sakamoto E , Koganei M , Sasaki H , Nagashima Y , Amo K , Aoki K , Morimoto C , Takeda E , Terauchi Y
Ref : Diabetes , 60 :1246 , 2011
Abstract : OBJECTIVE: Diet composition alters the metabolic states of adipocytes and hepatocytes in diabetes. The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation and fatty liver have been obscure. We investigated the extrapancreatic effects of DPP-4 inhibition on visceral fat and the liver. RESEARCH DESIGN AND METHODS: We investigated diet-induced metabolic changes in beta-cell-specific glucokinase haploinsufficient (Gck(+/-)) diabetic mice. We challenged animals with a diet containing a combination of sucrose and oleic acid (SO) or sucrose and linoleic acid (SL). Next, we assessed the effects of a DPP-4 inhibitor, des-fluoro-sitagliptin, on adipose tissue inflammation and hepatic steatosis. RESULTS: The epididymal fat weight and serum leptin level were significantly higher in Gck(+/-) mice fed SL than in mice fed SO, although no significant differences in body weight or adipocyte size were noted. Compared with SO, SL increased the numbers of CD11c(+) M1 macrophages and CD8(+) T-cells in visceral adipose tissue and the expression of E-selectin, P-selectin, and plasminogen activator inhibitor-1 (PAI-1). DPP-4 inhibition significantly prevented adipose tissue infiltration by CD8(+) T-cells and M1 macrophages and decreased the expression of PAI-1. The production of cytokines by activated T-cells was not affected by DPP-4 inhibition. Furthermore, DPP-4 inhibition prevented fatty liver in both wild-type and Gck(+/-) mice. DPP-4 inhibition also decreased the expressions of sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase-1, and fatty acid synthase, and increased the expression of peroxisome proliferator-activated receptor-alpha in the liver. CONCLUSIONS: Our findings indicated that DPP-4 inhibition has extrapancreatic protective effects against diet-induced adipose tissue inflammation and hepatic steatosis.
ESTHER : Shirakawa_2011_Diabetes_60_1246
PubMedSearch : Shirakawa_2011_Diabetes_60_1246
PubMedID: 21330637

Title : Broken sperm, cytoplasmic droplets and reduced sperm motility are principal markers of decreased sperm quality due to organophosphorus pesticides in rats - Okamura_2009_J.Occup.Health_51_478
Author(s) : Okamura A , Kamijima M , Ohtani K , Yamanoshita O , Nakamura D , Ito Y , Miyata M , Ueyama J , Suzuki T , Imai R , Takagi K , Nakajima T
Ref : J Occup Health , 51 :478 , 2009
Abstract : OBJECTIVES: Recent reports have shown significant associations between organopshophorus pesticide (OP) exposure and decreased sperm motility in workers and laboratory animals. However, the notion that OPs possess spermatotoxicity has yet to be established. The aim of this study was to clarify the effects of OP exposure on detailed sperm toxicity markers, i.e., motility, morphology and sperm adenine nucleotide contents, and the histopathology of the testis and epididymis. METHODS: Ten-week-old Wistar rats were divided into 4 groups (n=10) and orally administered corn oil, dichlorvos (DDVP; 5, 10 mg/kg) or diazinon (DZN; 3 mg/kg) 6 days a week for 9 wk. Sperm motility and morphology markers were analyzed with a computer-assisted sperm analysis (CASA) system. RESULTS: In addition to a significant decrease in acetylcholinesterase (AChE) activities and a significant increase in urinary OP metabolites, DDVP and DZN significantly reduced sperm motility, but they did not influence sperm adenine nucleotide contents. The OPs also significantly increased the percentage of broken sperm, and DDVP significantly increased the percentage of cytoplasmic droplets. Importantly, both OPs significantly increased cytoplasmic vacuolation and nuclear shrinkage in the epithelial cells of the ductus epididymis, whereas the testes did not show significant histopathological changes. CONCLUSIONS: The broken sperm and cytoplasmic droplets as well as reduced sperm motility were the relevant spermatotoxicity makers of DDVP and DZN. To our knowledge, this is the first report to suggest that the above-mentioned OP-induced spermatotoxicity is related to histopathological impairment of the caput epididymis.
ESTHER : Okamura_2009_J.Occup.Health_51_478
PubMedSearch : Okamura_2009_J.Occup.Health_51_478
PubMedID: 19779279

Title : [Treatment approach to congenital myasthenic syndrome in a patient with acetylcholine receptor deficiency] - Ishigaki_2009_No.To.Hattatsu_41_37
Author(s) : Ishigaki K , Murakami T , Ito Y , Yanagisawa A , Kodaira K , Shishikura K , Suzuki H , Hirayama Y , Osawa M
Ref : No To Hattatsu , 41 :37 , 2009
Abstract : Congenital myasthenic syndromes (CMS) are rare heterogeneous disorders of neurotransmission caused by genetic defects of neuromuscular junction molecules. While CMS patients have been reported worldwide, in Japan there have been only a few descriptions of adult CMS patients with acetylcholinesterase (AChE) deficiency and slow channel syndrome. Herein, we report a Japanese CMS patient with acetylcholine receptor (AChR) deficiency, diagnosed during childhood, and our treatment approach to the patient. This 13-year-old Japanese boy had had severe myasthenic symptoms since infancy. Ptosis, his first symptom, appeared at 5 months and nasal voice was recognized at 2 years of age. AchR and anti-muscle-specific tyrosine kinase (Musk) antibody remained negative. A positive tensilon test and decremental response on electromyogram supported the diagnosis of sero-negative myasthenia gravis. Despite thymectomy and strong immunosuppressive therapy including steroid pulse and FK 506, he gradually deteriorated and became wheelchair bound. Genetic analyses for AchR, Rapsyn, Musk and AChE were negative. At age 11 years, a muscle biopsy was performed in the deltoid muscle for neuromuscular junction sampling. Electron microscopic and confocal microscopic analysis of endplates showed almost complete loss of AChR and the diagnosis of CMS with AChR deficiency was confirmed. All immunosuppressive therapies were discontinued. Instead, we started Ubretide and 3,4-diaminopyridine (DAP) after obtaining informed consent. Although not approved in Japan for this use, 3,4-DAP is reportedly effective in refractory cases of CMS. The patient experienced no side effects. Despite all of the objective data were improving, his subjective symptoms and ADL remained poor. There are still many challenges in the treatment of the patient.
ESTHER : Ishigaki_2009_No.To.Hattatsu_41_37
PubMedSearch : Ishigaki_2009_No.To.Hattatsu_41_37
PubMedID: 19172815

Title : The Rice Annotation Project Database (RAP-DB): 2008 update - Tanaka_2008_Nucleic.Acids.Res_36_D1028
Author(s) : Tanaka T , Antonio BA , Kikuchi S , Matsumoto T , Nagamura Y , Numa H , Sakai H , Wu J , Itoh T , Sasaki T , Aono R , Fujii Y , Habara T , Harada E , Kanno M , Kawahara Y , Kawashima H , Kubooka H , Matsuya A , Nakaoka H , Saichi N , Sanbonmatsu R , Sato Y , Shinso Y , Suzuki M , Takeda J , Tanino M , Todokoro F , Yamaguchi K , Yamamoto N , Yamasaki C , Imanishi T , Okido T , Tada M , Ikeo K , Tateno Y , Gojobori T , Lin YC , Wei FJ , Hsing YI , Zhao Q , Han B , Kramer MR , McCombie RW , Lonsdale D , O'Donovan CC , Whitfield EJ , Apweiler R , Koyanagi KO , Khurana JP , Raghuvanshi S , Singh NK , Tyagi AK , Haberer G , Fujisawa M , Hosokawa S , Ito Y , Ikawa H , Shibata M , Yamamoto M , Bruskiewich RM , Hoen DR , Bureau TE , Namiki N , Ohyanagi H , Sakai Y , Nobushima S , Sakata K , Barrero RA , Souvorov A , Smith-White B , Tatusova T , An S , An G , S OO , Fuks G , Messing J , Christie KR , Lieberherr D , Kim H , Zuccolo A , Wing RA , Nobuta K , Green PJ , Lu C , Meyers BC , Chaparro C , Piegu B , Panaud O , Echeverria M
Ref : Nucleic Acids Research , 36 :D1028 , 2008
Abstract : The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: and
ESTHER : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedSearch : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedID: 18089549
Gene_locus related to this paper: orysa-Q9FW17 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q5N7L1 , orysa-pir7a , orysa-q2qyj1 , orysj-q6yse8 , orysa-q6yzk1 , orysa-Q8S0U8 , orysa-q33aq0 , orysa-Q0J0A4 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-b9fkb0 , orysj-cgep , orysj-q0djj0 , orysj-q0dud7 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1 , orysj-pla4 , orysj-pla1

Title : PPARalpha- and DEHP-Induced Cancers - Ito_2008_PPAR.Res_2008_759716
Author(s) : Ito Y , Nakajima T
Ref : PPAR Res , 2008 :759716 , 2008
Abstract : Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer and a potentially nongenotoxic carcinogen. Its mechanism had been earlier proposed based on peroxisome proliferator-activated receptor alpha (PPARalpha) because metabolites of DEHP are agonists. However, recent evidence also suggests the involvement of non-PPARalpha multiple pathway in DEHP-induced carcinogenesis. Since there are differences in the function and constitutive expression of PPARalpha among rodents and humans, species differences are also thought to exist in the carcinogenesis. However, species differences were also seen in the lipase activity involved in the first step of the DEHP metabolism, which should be considered in DEHP-induced carcinogenesis. Taken together, it is very difficult to extrapolate the results from rodents to humans in the case of DEHP carcinogenicity. However, PPARalpha-null mice or mice with human PPARalpha gene have been developed, which may lend support to make such a difficult extrapolation. Overall, further mechanical study on DEHP-induced carcinogenicity is warranted using these mice.
ESTHER : Ito_2008_PPAR.Res_2008_759716
PubMedSearch : Ito_2008_PPAR.Res_2008_759716
PubMedID: 18769559

Title : Permethrin may induce adult male mouse reproductive toxicity due to cis isomer not trans isomer - Zhang_2008_Toxicology_248_136
Author(s) : Zhang SY , Ueyama J , Ito Y , Yanagiba Y , Okamura A , Kamijima M , Nakajima T
Ref : Toxicology , 248 :136 , 2008
Abstract : Permethrin, the most popular insecticide among the synthetic pyrethroids, has been used worldwide to control a wide range of insects in agriculture, forestry, public health, and homes. Humans may have suffered potential exposure to this compound. The commercial formulation of permethrin contains trans and cis isomers. Here, at the same dosage, we made a comparison of the reproductive effects between these two isomers. Male adult ICR mice were orally administered trans- or cis-permethrin daily for 6 weeks at a dose of 0 or 70 mg/(kg day). In the cis-permethrin exposure group, the caudal epididymal sperm count and sperm motility were significantly reduced, and testosterone levels in testes and plasma also fell. Moreover, cis-permethrin induced abnormal seminiferous tubules in testes and suppressed testicular mRNA expression levels of peripheral benzodiazepine receptor, steroidogenic acute regulatory protein, and the cytochrome P450 side-chain cleavage enzyme. Although such adverse effects were not observed in the trans-permethrin exposure group, testicular and urinary metabolite 3-phenoxybenzoic acid levels in trans-permethrin-exposed mice were about three- and sevenfold higher than those in cis-permethrin-exposed mice, respectively. Furthermore, in vitro, hepatic microsomal hydrolase activity for trans-permethrin was nearly 62-fold higher than that for cis-permethrin. Taken together, the difference in metabolic activity between cis- and trans-permethrin might contribute to the difference in the reproductive toxicity between both isomers.
ESTHER : Zhang_2008_Toxicology_248_136
PubMedSearch : Zhang_2008_Toxicology_248_136
PubMedID: 18455858

Title : Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana - Itoh_2007_Genome.Res_17_175
Author(s) : Itoh T , Tanaka T , Barrero RA , Yamasaki C , Fujii Y , Hilton PB , Antonio BA , Aono H , Apweiler R , Bruskiewich R , Bureau T , Burr F , Costa de Oliveira A , Fuks G , Habara T , Haberer G , Han B , Harada E , Hiraki AT , Hirochika H , Hoen D , Hokari H , Hosokawa S , Hsing YI , Ikawa H , Ikeo K , Imanishi T , Ito Y , Jaiswal P , Kanno M , Kawahara Y , Kawamura T , Kawashima H , Khurana JP , Kikuchi S , Komatsu S , Koyanagi KO , Kubooka H , Lieberherr D , Lin YC , Lonsdale D , Matsumoto T , Matsuya A , McCombie WR , Messing J , Miyao A , Mulder N , Nagamura Y , Nam J , Namiki N , Numa H , Nurimoto S , O'Donovan C , Ohyanagi H , Okido T , Oota S , Osato N , Palmer LE , Quetier F , Raghuvanshi S , Saichi N , Sakai H , Sakai Y , Sakata K , Sakurai T , Sato F , Sato Y , Schoof H , Seki M , Shibata M , Shimizu Y , Shinozaki K , Shinso Y , Singh NK , Smith-White B , Takeda J , Tanino M , Tatusova T , Thongjuea S , Todokoro F , Tsugane M , Tyagi AK , Vanavichit A , Wang A , Wing RA , Yamaguchi K , Yamamoto M , Yamamoto N , Yu Y , Zhang H , Zhao Q , Higo K , Burr B , Gojobori T , Sasaki T
Ref : Genome Res , 17 :175 , 2007
Abstract : We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene.
ESTHER : Itoh_2007_Genome.Res_17_175
PubMedSearch : Itoh_2007_Genome.Res_17_175
PubMedID: 17210932
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9FYP7 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-cbp3 , orysa-cbpx , orysa-Q6YSZ8 , orysa-Q9FW17 , orysa-Q84QZ6 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q658B2 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-pir7a , orysa-q2qnj4 , orysa-q2qyj1 , orysa-q2r077 , orysa-Q4VWY7 , orysa-q5smv5 , orysa-q5z901 , orysa-Q5ZBI5 , orysa-q6atz0 , orysa-q6i5q3 , orysa-q6j657 , orysa-q6k4q2 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q8LQS5 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8W3C6 , orysa-Q9LHX5 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q69j38 , orysa-q69y21 , orysa-q75hy1 , orysa-q75hy2 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q652g4 , orysa-q688m8 , orysa-Q6H8G1 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q0jhi5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1

Title : Application of dual counter-current chromatography for rapid sample preparation of N-methylcarbamate pesticides in vegetable oil and citrus fruit - Ito_2006_J.Chromatogr.A_1108_20
Author(s) : Ito Y , Goto T , Yamada S , Matsumoto H , Oka H , Takahashi N , Nakazawa H , Nagase H
Ref : Journal of Chromatography A , 1108 :20 , 2006
Abstract : Dual counter-current chromatography (dual CCC) has been successfully applied to rapid sample preparation for the simultaneous determination of residual carbaryl, fenobucarb and methomyl in vegetable oil and citrus fruit. The citrus fruit samples were extracted with n-hexane solution containing stable isotopically labeled internal standards (methomyl-d3, fenobucarb-d3 and carbaryl-d9), and applied to dual CCC using a two-phase solvent system of n-hexane-acetonitrile to purify the carbamate pesticides from aliphatic sample matrix. The coiled column was rotated at 420 rpm, the lower mobile phase was introduced through the head toward the tail, and the upper mobile phase in the opposite direction. Due to the high partition efficiency of dual CCC, the lower phase fraction collected from 2 to 5 min after injection could be subjected to flow-injection tandem mass spectrometry directly after concentration. Repetitive sample injection can be performed at high reproducibility without a risk of contamination from the compounds retained in the column.
ESTHER : Ito_2006_J.Chromatogr.A_1108_20
PubMedSearch : Ito_2006_J.Chromatogr.A_1108_20
PubMedID: 16445929

Title : Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets - Ito_2005_Arch.Toxicol_79_147
Author(s) : Ito Y , Yokota H , Wang R , Yamanoshita O , Ichihara G , Wang H , Kurata Y , Takagi K , Nakajima T
Ref : Archives of Toxicology , 79 :147 , 2005
Abstract : To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6-3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2-14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor alpha involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.
ESTHER : Ito_2005_Arch.Toxicol_79_147
PubMedSearch : Ito_2005_Arch.Toxicol_79_147
PubMedID: 15798888

Title : The genome sequence and structure of rice chromosome 1 - Sasaki_2002_Nature_420_312
Author(s) : Sasaki T , Matsumoto T , Yamamoto K , Sakata K , Baba T , Katayose Y , Wu J , Niimura Y , Cheng Z , Nagamura Y , Antonio BA , Kanamori H , Hosokawa S , Masukawa M , Arikawa K , Chiden Y , Hayashi M , Okamoto M , Ando T , Aoki H , Arita K , Hamada M , Harada C , Hijishita S , Honda M , Ichikawa Y , Idonuma A , Iijima M , Ikeda M , Ikeno M , Ito S , Ito T , Ito Y , Iwabuchi A , Kamiya K , Karasawa W , Katagiri S , Kikuta A , Kobayashi N , Kono I , Machita K , Maehara T , Mizuno H , Mizubayashi T , Mukai Y , Nagasaki H , Nakashima M , Nakama Y , Nakamichi Y , Nakamura M , Namiki N , Negishi M , Ohta I , Ono N , Saji S , Sakai K , Shibata M , Shimokawa T , Shomura A , Song J , Takazaki Y , Terasawa K , Tsuji K , Waki K , Yamagata H , Yamane H , Yoshiki S , Yoshihara R , Yukawa K , Zhong H , Iwama H , Endo T , Ito H , Hahn JH , Kim HI , Eun MY , Yano M , Jiang J , Gojobori T
Ref : Nature , 420 :312 , 2002
Abstract : The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.
ESTHER : Sasaki_2002_Nature_420_312
PubMedSearch : Sasaki_2002_Nature_420_312
PubMedID: 12447438
Gene_locus related to this paper: orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5NA74 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q94D81 , orysa-cbp , orysa-Q5VQE5 , orysa-Q8RZ95 , orysa-Q9AWW1 , orysa-Q9AS70 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q943F9 , orysa-B9EWJ8 , orysa-Q5N8H1 , orysa-Q5NAI4 , orysa-Q94DP8 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q5N7J6 , orysa-Q8RYV9 , orysa-Q5SNH3 , orysa-Q94DD0 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-Q4VWY7 , orysa-q5jlm9 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5vnp5 , orysa-Q5VP27 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-q5zc23 , orysa-Q5ZCR3 , orysa-Q8L562 , orysa-Q8L570 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q9LHX5 , orysa-Q94E46 , orysa-Q656F2 , orysi-a2wn01 , orysi-b8a7e6 , orysi-b8a7e7 , orysj-b9eya5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q94d71

Title : Comparative studies of muscarinic and dopamine receptors in three strains of rat - Lim_1989_Eur.J.Pharmacol_165_279
Author(s) : Lim DK , Ito Y , Hoskins B , Rockhold RW , Ho IK
Ref : European Journal of Pharmacology , 165 :279 , 1989
Abstract : Cholinesterase activities and characteristics of muscarinic and dopamine receptors from 9 week old male Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were studied. Plasma cholinesterase activity in WKY was significantly lower (50%) than activity in the other strains. In studies of muscarinic receptors, the number of [3H]QNB binding sites in striata from SD rats was lower (18%) than those from WKY and SHR. However, muscarinic receptor properties (Kd and Bmax) were the same in hypothalami. Studies of dopamine receptors revealed that the densities of both D-1 and D-2 receptors in both striata and hypothalami were significantly higher in SHR than in other strains. However, there were no differences in the affinity constant (Kd). The higher densities in hypothalami from SHR were mainly due to the high population of D-1 and D-2 receptors in the posterior hypothalamus. In the anterior hypothalamus, there was no difference in the population of D-2 receptors. These results provide a substantive basis, i.e. demonstration of alterations in drug metabolizing enzymes and receptor populations, on which to build an understanding of the genetic predisposition to the actions of xenobiotic agents.
ESTHER : Lim_1989_Eur.J.Pharmacol_165_279
PubMedSearch : Lim_1989_Eur.J.Pharmacol_165_279
PubMedID: 2673798

Title : Acetylcholine in human muscle -
Author(s) : Ito Y , Miledi R , Molenaar PC , Vincent A , Polak RL , van Gelder M , Davis JN
Ref : Proc R Soc Lond B Biol Sci , 192 :475 , 1976
PubMedID: 4804