Saito K

References (19)

Title : Structure-Based Characterization and Improvement of an Enzymatic Activity of Acremonium alcalophilum Feruloyl Esterase - Phienluphon_2024_ACS.Sustain.Chem.Eng__
Author(s) : Phienluphon A , Kondo K , Mikami B , Teo KSK , Saito K , Watanabe T , Nagata T , Katahira M
Ref : ACS Sustainable Chem Eng , : , 2024
Abstract : Bacteria and fungi utilize carbohydrate-active enzymes, such as feruloyl esterases (FAEs), to degrade lignocellulosic biomass. FAEs in subfamily 5 (SF5) of carbohydrate esterase family 1 target larger substrates, making them particularly interesting. However, their mechanisms are not well understood due to limited structural information. This study presents the first structure of the catalytic domain (CD) of an SF5 FAE from Acremonium alcalophilum (AaFaeD), both free and in a complex with ferulic acid (FA). FA binds within a hydrophobic cleft formed by two hydrophobic walls facing each other. Structure-based functional mutagenesis of key residues in these walls clarified their roles in catalysis. Notably, the F120Y mutant of the AaFaeD catalytic domain (AaFaeD-CD) showed a 1.5-fold increase in catalytic activity toward methyl ferulate compared with the wild type. Structural comparisons with SF2 and SF3 FAEs revealed a more open substrate-binding site in SF5. High-performance liquid chromatography and gas chromatographymass spectrometry analysis of destarched wheat bran hydrolysis by AaFaeD-CD showed that SF5 FAEs can process both monomeric and dimeric phenolic substrates, like 5,5'-dehydrodiferulate, unlike SF2 and SF3 FAEs, which prefer monomeric substrates.
ESTHER : Phienluphon_2024_ACS.Sustain.Chem.Eng__
PubMedSearch : Phienluphon_2024_ACS.Sustain.Chem.Eng__
Gene_locus related to this paper: sodal-AaFaeD

Title : Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses - Ishiura_2014_J.Hum.Genet_59_163
Author(s) : Ishiura H , Takahashi Y , Hayashi T , Saito K , Furuya H , Watanabe M , Murata M , Suzuki M , Sugiura A , Sawai S , Shibuya K , Ueda N , Ichikawa Y , Kanazawa I , Goto J , Tsuji S
Ref : J Hum Genet , 59 :163 , 2014
Abstract : Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP.
ESTHER : Ishiura_2014_J.Hum.Genet_59_163
PubMedSearch : Ishiura_2014_J.Hum.Genet_59_163
PubMedID: 24451228
Gene_locus related to this paper: human-SPG21

Title : Total cholesterol level for assessing pancreatic insufficiency due to chronic pancreatitis - Hirano_2014_Gut.Liver_8_563
Author(s) : Hirano K , Saito T , Mizuno S , Tada M , Sasahira N , Isayama H , Matsukawa M , Umefune G , Akiyama D , Saito K , Kawahata S , Takahara N , Uchino R , Hamada T , Miyabayashi K , Mohri D , Sasaki T , Kogure H , Yamamoto N , Nakai Y , Koike K
Ref : Gut Liver , 8 :563 , 2014
Abstract : BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice.
METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups.
RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052).
CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.
ESTHER : Hirano_2014_Gut.Liver_8_563
PubMedSearch : Hirano_2014_Gut.Liver_8_563
PubMedID: 25228979

Title : Immobilization of an esterase inhibitor on a porous hollow-fiber membrane by radiation-induced graft polymerization for developing a diagnostic tool for feline kidney diseases - Matsuno_2013_Biosci.Biotechnol.Biochem_77_2061
Author(s) : Matsuno S , Umeno D , Miyazaki M , Suzuta Y , Saito K , Yamashita T
Ref : Biosci Biotechnol Biochem , 77 :2061 , 2013
Abstract : Removal of the major urinary protein, cauxin, a carboxylesterase, from cat urine is essential for distinguishing between physiological and abnormal proteinuria by a urine dipstick. We have previously developed a material for removing cauxin by using lens culinaris agglutinin (LCA) lectin which targets the N-linked oligosaccharides present in cauxin. To improve the affinity and specificity toward cauxin, we immobilized 1,1,1-trifluoro-3-(2-sulfanylethylsulfanyl) propane-2-one, an inhibitor of esterases, to a polymer chain grafted on to a porous hollow-fiber membrane by applying radiation-induced graft polymerization. Normal male urine was forced to permeate through the pores rimmed by the ligand-immobilized polymer chain. Cauxin could not be detected in the effluent from the membrane. The residence time of the urine across a membrane thickness of 1 mm was set at 7 s. The respective dynamic and equilibrium binding capacities of the membrane for cauxin were 2 and 3 mg/g. The developed cauxin-affinity membrane material was more effective for diagnosing cat kidney diseases than the LCA lectin tip.
ESTHER : Matsuno_2013_Biosci.Biotechnol.Biochem_77_2061
PubMedSearch : Matsuno_2013_Biosci.Biotechnol.Biochem_77_2061
PubMedID: 24096669

Title : IL-6 attenuates trimethyltin-induced cognitive dysfunction via activation of JAK2\/STAT3, M1 mAChR and ERK signaling network - Kim_2013_Cell.Signal_25_1348
Author(s) : Kim BK , Tran HY , Shin EJ , Lee C , Chung YH , Jeong JH , Bach JH , Kim WK , Park DH , Saito K , Nabeshima T , Kim HC
Ref : Cell Signal , 25 :1348 , 2013
Abstract : We previously reported that interleukin (IL)-6 deficiency potentiates trimethyltin (TMT)-induced convulsive neurotoxicity. The purpose in this study was to investigate the molecular mechanism by which cytokines affect TMT-induced cognitive impairment. To accomplish this, we examined hippocampal changes in Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in relation to cholinergic parameters after TMT treatment in mice genetically deficient in IL-6 (IL-6(-/-)), tumor necrosis factor-alpha (TNF-alpha(-/-)), or interferon-gamma (IFN-gamma(-/-)). The IL-6(-/-) mice were the most susceptible to TMT-induced cognitive dysfunction and exhibited significant decreases in JAK2/STAT3 signaling and M1 muscarinic acetylcholine receptor (mAChR) expression, as well as other cholinergic parameters, compared with wild-type (WT) animals. Recombinant IL-6 protein (rIL-6) significantly attenuated these impairments in TMT-treated IL-6(-/-) mice, whereas an IL-6 receptor antibody potentiated these impairments in TMT-treated WT animals. Inhibition of JAK2 with AG490 or inhibition of cholinergic signaling with the M1 mAChR antagonist dicyclomine counteracted the attenuating effects of rIL-6 on phosphorylated extracellular signal-regulated kinase (ERK) expression, or on cognitive impairment in TMT-treated IL-6(-/-) mice. However, neither AG490 nor dicyclomine significantly attenuated effects of rIL-6 on acetylcholinesterase values. Our results suggest that activation of JAK2/STAT3 signaling and upregulation of the M1 mAChR are essential components of IL-6-mediated memory improvement against TMT toxicity.
ESTHER : Kim_2013_Cell.Signal_25_1348
PubMedSearch : Kim_2013_Cell.Signal_25_1348
PubMedID: 23499905

Title : Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant symbiosis - Tisserant_2013_Proc.Natl.Acad.Sci.U.S.A_110_20117
Author(s) : Tisserant E , Malbreil M , Kuo A , Kohler A , Symeonidi A , Balestrini R , Charron P , Duensing N , Frei dit Frey N , Gianinazzi-Pearson V , Gilbert LB , Handa Y , Herr JR , Hijri M , Koul R , Kawaguchi M , Krajinski F , Lammers PJ , Masclaux FG , Murat C , Morin E , Ndikumana S , Pagni M , Petitpierre D , Requena N , Rosikiewicz P , Riley R , Saito K , San Clemente H , Shapiro H , van Tuinen D , Becard G , Bonfante P , Paszkowski U , Shachar-Hill YY , Tuskan GA , Young JP , Sanders IR , Henrissat B , Rensing SA , Grigoriev IV , Corradi N , Roux C , Martin F
Ref : Proc Natl Acad Sci U S A , 110 :20117 , 2013
Abstract : The mutualistic symbiosis involving Glomeromycota, a distinctive phylum of early diverging Fungi, is widely hypothesized to have promoted the evolution of land plants during the middle Paleozoic. These arbuscular mycorrhizal fungi (AMF) perform vital functions in the phosphorus cycle that are fundamental to sustainable crop plant productivity. The unusual biological features of AMF have long fascinated evolutionary biologists. The coenocytic hyphae host a community of hundreds of nuclei and reproduce clonally through large multinucleated spores. It has been suggested that the AMF maintain a stable assemblage of several different genomes during the life cycle, but this genomic organization has been questioned. Here we introduce the 153-Mb haploid genome of Rhizophagus irregularis and its repertoire of 28,232 genes. The observed low level of genome polymorphism (0.43 SNP per kb) is not consistent with the occurrence of multiple, highly diverged genomes. The expansion of mating-related genes suggests the existence of cryptic sex-related processes. A comparison of gene categories confirms that R. irregularis is close to the Mucoromycotina. The AMF obligate biotrophy is not explained by genome erosion or any related loss of metabolic complexity in central metabolism, but is marked by a lack of genes encoding plant cell wall-degrading enzymes and of genes involved in toxin and thiamine synthesis. A battery of mycorrhiza-induced secreted proteins is expressed in symbiotic tissues. The present comprehensive repertoire of R. irregularis genes provides a basis for future research on symbiosis-related mechanisms in Glomeromycota.
ESTHER : Tisserant_2013_Proc.Natl.Acad.Sci.U.S.A_110_20117
PubMedSearch : Tisserant_2013_Proc.Natl.Acad.Sci.U.S.A_110_20117
PubMedID: 24277808
Gene_locus related to this paper: rhiid-u9u175 , rhiid-u9trg1 , rhiid-u9uh96 , rhiid-u9ttu4

Title : MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats - Takashina_2008_J.Neural.Transm.(Vienna)_115_1027
Author(s) : Takashina K , Bessho T , Mori R , Eguchi J , Saito K
Ref : J Neural Transm (Vienna) , 115 :1027 , 2008
Abstract : The effect of MKC-231 on acetylcholine (ACh) synthesis and release was studied in the hippocampus of normal and AF64A-treated rats. AF64A (3 nmol/brain, i.c.v.) produced significant reduction of high-affinity choline uptake (HACU) and high K+-induced ACh release in hippocampal synaptosomes. Treatments with MKC-231 (10(-8) and 10(-7) M) showed significant reverse of the decrease in both HACU and ACh release. In hippocampal slices superfused with choline-containing artificial cerebro-spinal fluid (ACSF), high K+-induced ACh release was gradually decreased by repeated alteration of resting and high K+ stimulations in AF64A-treated rats. However, addition of MKC-231 (10(-8) to 10(-7) M) in the superfusate reduces this decrease. In vivo microdialysis studies indicate MKC-231 (10 mg/kg, p.o.) significantly reversed reduction of basal ACh concentrations in AF64A-treated rats, measured by radioimmunoassay without a cholinesterase inhibitor in the perfusate. These results indicate MKC-231 improves AF64A-induced cholinergic hypofunction by enhancing HACU, subsequently facilitating ACh synthesis and release in vitro and in vivo.
ESTHER : Takashina_2008_J.Neural.Transm.(Vienna)_115_1027
PubMedSearch : Takashina_2008_J.Neural.Transm.(Vienna)_115_1027
PubMedID: 18446264

Title : Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries - Otsuki_2005_DNA.Res_12_117
Author(s) : Otsuki T , Ota T , Nishikawa T , Hayashi K , Suzuki Y , Yamamoto J , Wakamatsu A , Kimura K , Sakamoto K , Hatano N , Kawai Y , Ishii S , Saito K , Kojima S , Sugiyama T , Ono T , Okano K , Yoshikawa Y , Aotsuka S , Sasaki N , Hattori A , Okumura K , Nagai K , Sugano S , Isogai T
Ref : DNA Research , 12 :117 , 2005
Abstract : We have developed an in silico method of selection of human full-length cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. Fullness rates were increased to about 80% by combination of the oligo-capping method and ATGpr, software for prediction of translation start point and the coding potential. Then, using 5'-end single-pass sequences, cDNAs having the signal sequence were selected by PSORT ('signal sequence trap'). We also applied 'secretion or membrane protein-related keyword trap' based on the result of BLAST search against the SWISS-PROT database for the cDNAs which could not be selected by PSORT. Using the above procedures, 789 cDNAs were primarily selected and subjected to full-length sequencing, and 334 of these cDNAs were finally selected as novel. Most of the cDNAs (295 cDNAs: 88.3%) were predicted to encode secretion or membrane proteins. In particular, 165(80.5%) of the 205 cDNAs selected by PSORT were predicted to have signal sequences, while 70 (54.2%) of the 129 cDNAs selected by 'keyword trap' preserved the secretion or membrane protein-related keywords. Many important cDNAs were obtained, including transporters, receptors, and ligands, involved in significant cellular functions. Thus, an efficient method of selecting secretion or membrane protein-encoding cDNAs was developed by combining the above four procedures.
ESTHER : Otsuki_2005_DNA.Res_12_117
PubMedSearch : Otsuki_2005_DNA.Res_12_117
PubMedID: 16303743

Title : Complete sequencing and characterization of 21,243 full-length human cDNAs - Ota_2004_Nat.Genet_36_40
Author(s) : Ota T , Suzuki Y , Nishikawa T , Otsuki T , Sugiyama T , Irie R , Wakamatsu A , Hayashi K , Sato H , Nagai K , Kimura K , Makita H , Sekine M , Obayashi M , Nishi T , Shibahara T , Tanaka T , Ishii S , Yamamoto J , Saito K , Kawai Y , Isono Y , Nakamura Y , Nagahari K , Murakami K , Yasuda T , Iwayanagi T , Wagatsuma M , Shiratori A , Sudo H , Hosoiri T , Kaku Y , Kodaira H , Kondo H , Sugawara M , Takahashi M , Kanda K , Yokoi T , Furuya T , Kikkawa E , Omura Y , Abe K , Kamihara K , Katsuta N , Sato K , Tanikawa M , Yamazaki M , Ninomiya K , Ishibashi T , Yamashita H , Murakawa K , Fujimori K , Tanai H , Kimata M , Watanabe M , Hiraoka S , Chiba Y , Ishida S , Ono Y , Takiguchi S , Watanabe S , Yosida M , Hotuta T , Kusano J , Kanehori K , Takahashi-Fujii A , Hara H , Tanase TO , Nomura Y , Togiya S , Komai F , Hara R , Takeuchi K , Arita M , Imose N , Musashino K , Yuuki H , Oshima A , Sasaki N , Aotsuka S , Yoshikawa Y , Matsunawa H , Ichihara T , Shiohata N , Sano S , Moriya S , Momiyama H , Satoh N , Takami S , Terashima Y , Suzuki O , Nakagawa S , Senoh A , Mizoguchi H , Goto Y , Shimizu F , Wakebe H , Hishigaki H , Watanabe T , Sugiyama A , Takemoto M , Kawakami B , Watanabe K , Kumagai A , Itakura S , Fukuzumi Y , Fujimori Y , Komiyama M , Tashiro H , Tanigami A , Fujiwara T , Ono T , Yamada K , Fujii Y , Ozaki K , Hirao M , Ohmori Y , Kawabata A , Hikiji T , Kobatake N , Inagaki H , Ikema Y , Okamoto S , Okitani R , Kawakami T , Noguchi S , Itoh T , Shigeta K , Senba T , Matsumura K , Nakajima Y , Mizuno T , Morinaga M , Sasaki M , Togashi T , Oyama M , Hata H , Komatsu T , Mizushima-Sugano J , Satoh T , Shirai Y , Takahashi Y , Nakagawa K , Okumura K , Nagase T , Nomura N , Kikuchi H , Masuho Y , Yamashita R , Nakai K , Yada T , Ohara O , Isogai T , Sugano S
Ref : Nat Genet , 36 :40 , 2004
Abstract : As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.
ESTHER : Ota_2004_Nat.Genet_36_40
PubMedSearch : Ota_2004_Nat.Genet_36_40
PubMedID: 14702039
Gene_locus related to this paper: human-ABHD1 , human-ABHD4 , human-ABHD12 , human-ABHD16A , human-ACOT1 , human-LDAH , human-ABHD18 , human-CES1 , human-CES4A , human-CES5A , human-CPVL , human-DAGLB , human-EPHX2 , human-KANSL3 , human-LIPA , human-LPL , human-MEST , human-NDRG1 , human-NLGN1 , human-NLGN4X , human-PRCP , human-PRSS16 , human-SERAC1 , human-TMEM53

Title : The Drg-1 gene suppresses tumor metastasis in prostate cancer - Bandyopadhyay_2003_Cancer.Res_63_1731
Author(s) : Bandyopadhyay S , Pai SK , Gross SC , Hirota S , Hosobe S , Miura K , Saito K , Commes T , Hayashi S , Watabe M , Watabe K
Ref : Cancer Research , 63 :1731 , 2003
Abstract : Drg-1 was previously identified (N. van Belzen et al., Lab. Investig., 77: 85-92, 1997) as a gene that was up-regulated by the induction of differentiation in a colon carcinoma cell line in vitro. Subsequently, this gene was found to be regulated by several factors including hypoxia, androgen, p53, and N-myc. Recently, Drg-1 has also been shown to be involved in tumor progression in animals, although the clinical significance of its involvement remains to be investigated. To clarify the functional role of Drg-1 in prostate cancer, we examined a clinical archive of cancer specimens for the expression of Drg-1 by immunohistochemistry. We found that the expression of Drg-1 had a significant inverse correlation with the Gleason grading and the overall survival rate of patients. In particular, the gene expression in patients with lymph node or bone metastasis was significantly reduced as compared with those with localized prostate cancer, suggesting that the function of Drg-1 is negatively involved in metastatic progression of the disease. To further clarify the function of this gene in the advancement of prostate cancer, a spontaneous metastasis assay was performed in a severe combined immunodeficient (SCID) mouse model. We found that Drg-1 almost completely inhibited lung colonization of highly metastatic prostate cancer cells without affecting the growth of the primary tumors. These results strongly suggest that Drg-1 is a candidate metastasis suppressor gene for prostate cancer and may serve as a useful prognostic marker.
ESTHER : Bandyopadhyay_2003_Cancer.Res_63_1731
PubMedSearch : Bandyopadhyay_2003_Cancer.Res_63_1731
PubMedID: 12702552
Gene_locus related to this paper: human-NDRG1

Title : Enhancing effect of dimethyl sulfoxide on nociceptive transmission in isolated spinal cord of newborn rat - Kubota_1998_Eur.J.Pharmacol_351_173
Author(s) : Kubota K , Fujibayashi K , Saito K
Ref : European Journal of Pharmacology , 351 :173 , 1998
Abstract : The effect of dimethyl sulfoxide (DMSO) on the slow ventral root potential, which is related to nociceptive transmission, was investigated in the isolated spinal cord of a newborn rat. DMSO at 0.3-1% (v/v) enhanced the slow ventral root potential, but not mono- and polysynaptic reflex discharges. DMSO at 1% also enhanced the depolarization induced by substance P or capsaicin. In the presence of tetrodotoxin (0.3 microM), DMSO at 1% did not influence the substance P-induced depolarization but enhanced the acetylcholine-induced depolarization. Edrophonium at 10 microM also enhanced the slow ventral root potential, and the magnitude of the effect was comparable to that of 1% DMSO. In the presence of atropine (0.3 microM) and hexamethonium (30 microM), the effect of edrophonium disappeared, but half of the effect of DMSO remained. Artificial cerebrospinal fluid containing either 0.87% (w/v) urea or 4.6% (w/v) sucrose, which has the same osmotic pressure as that containing 1% DMSO, did not have the same effect as DMSO on the slow ventral root potential. In the saphenous nerve-dorsal root preparation, the compound action potential was enhanced by 4-aminopyridine (10 microM), but was not affected by DMSO up to 3%. The results suggest that DMSO enhances the slow ventral root potential through mechanisms based on the inhibition of cholinesterase activity and other action(s) involved in increasing transmitter release from nerve endings in nociceptive transmission pathways in the isolated spinal cord of the newborn rat. Neither the blockade of K+ channels nor hyperosmotic effects are likely mechanisms of DMSO action.
ESTHER : Kubota_1998_Eur.J.Pharmacol_351_173
PubMedSearch : Kubota_1998_Eur.J.Pharmacol_351_173
PubMedID: 9687000

Title : MCI-225, a novel thienopyrimidine analog, enhances attentional eye tracking in midpontine pretrigeminal preparation - Eguchi_1997_Pharmacol.Biochem.Behav_56_229
Author(s) : Eguchi J , Saitoh Y , Egawa M , Saito K , Kawamura H
Ref : Pharmacol Biochem Behav , 56 :229 , 1997
Abstract : The effects of MCI-225, a novel psychoactive compound, and reference drugs on attention behavior were studied using visual stimulus induced vertical eye tracking movements in midpontine pretrigeminal (PTG) feline preparation. Surgery was performed under ether anesthesia and subsequently switched to nitrous oxide-fluothane which was discontinued only during experimental sessions. In addition xylocaine was locally injected. Vertical eye movements were monitored by electrooculogram (EOG) and a TV camera. To compare the effects of drugs on eye movement, numbers of spontaneous and tracking eye movements exceeding a present amplitude in EOG were counted before and during the visual stimulation, respectively. MCI-225 (1 and 3 mg/kg, i.v.) enhanced tracking movements dose-dependently without an increase in spontaneous eye movements. No or little change of the electrocorticogram (ECoG) was seen with 1 mg/kg MCI-225 and a slight increase in low voltage fast pattern was observed with 3 mg/kg, i.v.. On the other hand, tacrine (0.3 mg/kg, i.v.), physostigmine (0.03 mg/kg, i.v.) and methylphenidate (0.3 mg/kg, i.v.) enhanced both types of eye movement and induced ECoG arousal. Desipramine (3 mg/kg, i.v.) slightly increased spontaneous eye movement without affecting tracking movements. Piracetam (100 mg/kg, i.v.) decreased spontaneous eye movements only. These data clearly show that MCI-225 enhances attention to a moving object and suggest that MCI-225 could be useful in the treatment of attentional deficits and related cognitive dysfunctions in psychiatric disorders.
ESTHER : Eguchi_1997_Pharmacol.Biochem.Behav_56_229
PubMedSearch : Eguchi_1997_Pharmacol.Biochem.Behav_56_229
PubMedID: 9050079

Title : Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice - Tani_1997_Psychopharmacology.(Berl)_129_225
Author(s) : Tani Y , Saito K , Tsuneyoshi A , Imoto M , Ohno T
Ref : Psychopharmacology (Berl) , 129 :225 , 1997
Abstract : The aim of the present study was to evaluate the effects of nicotinic acetylcholine receptor (nACh-R) agonists such as (-)-nicotine and related compounds on brain monoamine turnover. A single administration of (-)-nicotine (0.04, 0.2, 1.0, and 5.0 mg/kg SC) increased both noradrenaline (NA) and dopamine (DA) turnover in a dose-dependent manner, and the maximum effects were achieved 30 min after treatment with (-)-nicotine (1.0 mg/kg). The effect of (-)-nicotine on serotonin (5-HT) turnover was complicated; 5-HT turnover was increased at a low dose of (-)-nicotine (0.04 mg/kg) but decreased at a high dose (1.0 mg/kg). The (-)-nicotine (1.0 mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg i.p.) but not by hexamethonium (2.0 mg/kg i.p.). These findings indicate that systemically administered (-)-nicotine can enhance brain NA and DA turnover and affect 5-HT turnover, both of which are mediated by central nACh-R. The changes in the monoamine turnover induced by (+/-)-anabasine were similar to those induced by (-)-nicotine, while (-)-lobeline and (-)-cytisine had little effect, and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) increased NA and 5-HT turnover but not DA turnover at all doses tested. (S)-3-Methyl-5-(l-methyl-2- pyrrolidinyl)isoxazole (ABT-418), a selective neuronal nACh-R agonist, increased NA, DA and 5-HT turnover, but had a weaker effect on DA turnover than NA and 5-HT turnover. In addition, 9-amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholine esterase inhibitor, also increased monoamine turnover in the brain. Pretreatment with mecamylamine completely blocked the THA-induced increase in NA and 5-HT turnover, but not in DA turnover, suggesting that the nACh-R system is involved in the THA-induced increase in brain NA and 5-HT turnover. On the other hand, (-)-cytisine, a partial agonist for the beta 2 subunit containing nACh-R, completely inhibited the nACh-R agonist- and THA-induced increases in NA turnover, but not in DA turnover, and normalized the changes in 5-HT turnover. In conclusion, the subtypes of nACh-Rs mediating DA turnover may be different from those mediating NA and 5-HT turnover in the CNS.
ESTHER : Tani_1997_Psychopharmacology.(Berl)_129_225
PubMedSearch : Tani_1997_Psychopharmacology.(Berl)_129_225
PubMedID: 9084060

Title : Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3- b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats - Bessho_1996_Arzneimittelforschung_46_369
Author(s) : Bessho T , Takashina K , Tabata R , Ohshima C , Chaki H , Yamabe H , Egawa M , Tobe A , Saito K
Ref : Arzneimittelforschung , 46 :369 , 1996
Abstract : The pharmacological properties of MKC-231 (2-(2-oxopyrrolidin-1-yl)-N- (2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl) acetoamide, CAS 135463-81-9) in comparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40-8) were studied. MKC-231(10(-10)-10(-6) moll) significantly increased high affinity choline uptake (HACU) when it was incubated with the hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but not of normal rats. MKC-231 did not affect the AChE activity, [3H]- quinuclidinyl benzilate binding, and [3H]-pirenzepine binding. Oral administration of MKC-231 (1-10 mg/kg) significantly improved the learning deficits in the Morris' water maze of AF64A-treated rats, but it did not produce any significant side effects, like tremor, salivation or hypothermia, which were observed in rats treated with high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed to ameliorate the learning deficits in AF64A-treated rats. These results suggest that MKC-231 is a novel and quite unique compound, which improves the memory impairment induced by AF64A through the enhancement of HACU without any side effects at the effective doses.
ESTHER : Bessho_1996_Arzneimittelforschung_46_369
PubMedSearch : Bessho_1996_Arzneimittelforschung_46_369
PubMedID: 8740080

Title : Effects of MCI-225 on memory and glucose utilization in basal forebrain-lesioned rats - Eguchi_1995_Pharmacol.Biochem.Behav_51_935
Author(s) : Eguchi J , Iwai K , Yuasa T , Egawa M , Komatsu T , Saito K
Ref : Pharmacol Biochem Behav , 51 :935 , 1995
Abstract : The effects of MCI-225 on amnesia, the cerebral glucose metabolism, and choline acetyltransferase (ChAT) activity in basal forebrain (BF)-lesioned rats were studied in comparison with those of tacrine. Bilateral BF lesions with ibotenic acid impaired the performance in passive avoidance (PA) tasks. Single administration of MCI-225 (10 mg/kg, PO) after a 2-week postoperative recovery period, increased the escape latencies in the PA task, but was not statistically significant. Repeated administration of MCI-225 (0.3 and 1 mg/kg, PO for 6 days) significantly reversed the PA failure. The BF-lesioned rat exhibited a marked decrease in the local cerebral glucose utilization (LCGU) in the frontal cortex, parietal cortex, and caudate-putamen. MCI-225 (1 mg/kg, PO for 5 days) significantly ameliorated the reduction of the LCGU in the parietal cortex. MCI-225 did not change the decrease in the cortical ChAT activity induced by the BF lesion. Repeated administration of tacrine reversed the PA failure (0.3 mg/kg, PO) but failed to prevent the decrement in the LCGU and the ChAT activity. These results suggest that MCI-225 could be effective in the treatment of senile dementia of the Alzheimer type, which is accompanied with both deficit in the BF-cortex cholinergic neuron and cerebral glucose hypometabolism.
ESTHER : Eguchi_1995_Pharmacol.Biochem.Behav_51_935
PubMedSearch : Eguchi_1995_Pharmacol.Biochem.Behav_51_935
PubMedID: 7675880

Title : Alpha 1-adrenoceptors in the conduction system of rat hearts - Saito_1994_Br.J.Pharmacol_111_465
Author(s) : Saito K , Suetsugu T , Oku Y , Kuroda A , Tanaka H
Ref : British Journal of Pharmacology , 111 :465 , 1994
Abstract : 1. We have characterized alpha 1-adrenoceptor in the conduction systems of the rat heart by quantitative autoradiography. 2. Consecutive 20 micron thick sections from a single rat heart containing the sinoatrial (SA) node and atrioventricular (AV) node were incubated with increasing concentrations of [3H]-prazosin with or without 10 microM phentolamine. After exposure to 3H-Ultrofilm, optical densities corresponding to the SA node and AV node were determined by computerized densitometry after comparison with 3H standards. 3. The SA node and AV node were stained heavily for cholinesterase and they contained a higher concentration of alpha 1-adrenoceptors than the adjacent myocardium without a significant change in the affinity. 4. These results support the hypothesis that alpha 1-adrenoceptors may play an important role not only in inotropism but also in chronotropism of rat hearts.
ESTHER : Saito_1994_Br.J.Pharmacol_111_465
PubMedSearch : Saito_1994_Br.J.Pharmacol_111_465
PubMedID: 8004391

Title : Effect of synergists on the oral and topical toxicity of azamethiphos to organophosphate-resistant houseflies (Diptera: Muscidae) - Saito_1992_J.Econ.Entomol_85_1041
Author(s) : Saito K , Motoyama N , Dauterman WC
Ref : J Econ Entomol , 85 :1041 , 1992
Abstract : Dermal and oral toxicities of azamethiphos were determined in two organophosphate-resistant and one susceptible strain of houseflies, Musca domestica L. The 594vb strain was 1,967-fold more resistant to azamethiphos when compared with the susceptible Chemical Specialties Manufacturers Association (CSMA) strain by dermal application. When the compound was administered orally to the 594vb strain, we observed only a 15-fold resistance. In contrast, the Yachiyo strain, which show 1,500-fold resistance to diazinon and which has known multiple mechanisms for organophosphate resistance, showed only 6-fold resistance to azamethiphos by topical application and 4-fold resistance by oral administration. Azamethiphos administered dermally and orally was equally toxic to the CSMA and Yachiyo strains. However, when azamethiphos was administered to the 594vb strain, the insecticide was 71 times more toxic orally than by the dermal route. This result indicated involvement of a cuticular penetration factor in the resistance mechanism. The effect on azamethiphos toxicity of piperonyl butoxide (PB), an inhibitor of the monooxygenases, and tributylphosphorotrithioate (DEF), an esterase inhibitor, was investigated in the three strains. Pretreatment of the flies with PB, DEF, or PB+DEF before topical application of azamethiphos resulted in a significant decrease in LD50s in all the strains. The degree of synergism, however, varied depending upon the strains and the synergists. Similar results were obtained when azamethiphos was administered orally following pretreatment of the flies with PB+DEF. We attribute the high level of azamethiphos resistance in the 594vb strain partly to increased degradation by oxidative and hydrolytic enzymes. The hydrolytic enzymes are more important, but other factors including reduced cuticular penetration and insensitive acetylcholinesterase may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Saito_1992_J.Econ.Entomol_85_1041
PubMedSearch : Saito_1992_J.Econ.Entomol_85_1041
PubMedID: 1517504

Title : The cloning and expression of a gene encoding Old Yellow Enzyme from Saccharomyces carlsbergensis - Saito_1991_J.Biol.Chem_266_20720
Author(s) : Saito K , Thiele DJ , Davio M , Lockridge O , Massey V
Ref : Journal of Biological Chemistry , 266 :20720 , 1991
Abstract : We have identified a gene that encodes Old Yellow Enzyme in brewer's bottom yeast. The open reading frame encodes a polypeptide of 400 amino acids with Mr = 45,021. Using the T7 RNA polymerase system, recombinant enzyme was expressed in Escherichia coli. 17 mg of Old Yellow Enzyme was obtained from a 3-liter cell culture, and the recombinant enzyme had NADPH oxidase activity. On fast protein liquid chromatography separation, the recombinant enzyme showed a single large peak, while native enzyme from brewer's bottom yeast separated into five fractions on fast protein liquid chromatography. Southern blot analysis showed that there are at least two Old Yellow Enzyme genes in brewer's bottom yeast genomic DNA. These results suggest that the heterogeneity of Old Yellow Enzyme in Saccharomyces carlsbergensis is due to the presence of multiple genes.
ESTHER : Saito_1991_J.Biol.Chem_266_20720
PubMedSearch : Saito_1991_J.Biol.Chem_266_20720
PubMedID: 1939123

Title : Studies on soluble proteins released from the synaptic vesicles of rat brain cortex -
Author(s) : Matsuda T , Saito K , Katsuki S , Hata F , Yoshida H
Ref : Journal of Neurochemistry , 18 :713 , 1971