Nakajima Y

References (18)

Title : Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient with MODY-like Diabetes - Kondoh_2022_Tohoku.J.Exp.Med_256_37
Author(s) : Kondoh T , Nakajima Y , Yokoi K , Matsumoto Y , Inagaki H , Kato T , Ito T , Yoshikawa T , Kurahashi H
Ref : Tohoku J Exp Med , 256 :37 , 2022
Abstract : Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.
ESTHER : Kondoh_2022_Tohoku.J.Exp.Med_256_37
PubMedSearch : Kondoh_2022_Tohoku.J.Exp.Med_256_37
PubMedID: 35082198
Gene_locus related to this paper: human-CEL

Title : Dipeptidyl aminopeptidase IV from Stenotrophomonas maltophilia exhibits activity against a substrate containing a 4-hydroxyproline residue - Nakajima_2008_J.Bacteriol_190_7819
Author(s) : Nakajima Y , Ito K , Toshima T , Egawa T , Zheng H , Oyama H , Wu YF , Takahashi E , Kyono K , Yoshimoto T
Ref : Journal of Bacteriology , 190 :7819 , 2008
Abstract : The crystal structure of dipeptidyl aminopeptidase IV from Stenotrophomonas maltophilia was determined at 2.8-A resolution by the multiple isomorphous replacement method, using platinum and selenomethionine derivatives. The crystals belong to space group P4(3)2(1)2, with unit cell parameters a = b = 105.9 A and c = 161.9 A. Dipeptidyl aminopeptidase IV is a homodimer, and the subunit structure is composed of two domains, namely, N-terminal beta-propeller and C-terminal catalytic domains. At the active site, a hydrophobic pocket to accommodate a proline residue of the substrate is conserved as well as those of mammalian enzymes. Stenotrophomonas dipeptidyl aminopeptidase IV exhibited activity toward a substrate containing a 4-hydroxyproline residue at the second position from the N terminus. In the Stenotrophomonas enzyme, one of the residues composing the hydrophobic pocket at the active site is changed to Asn611 from the corresponding residue of Tyr631 in the porcine enzyme, which showed very low activity against the substrate containing 4-hydroxyproline. The N611Y mutant enzyme was generated by site-directed mutagenesis. The activity of this mutant enzyme toward a substrate containing 4-hydroxyproline decreased to 30.6% of that of the wild-type enzyme. Accordingly, it was considered that Asn611 would be one of the major factors involved in the recognition of substrates containing 4-hydroxyproline.
ESTHER : Nakajima_2008_J.Bacteriol_190_7819
PubMedSearch : Nakajima_2008_J.Bacteriol_190_7819
PubMedID: 18820015
Gene_locus related to this paper: xanma-P95782

Title : Novel inhibitor for prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis and details of substrate-recognition mechanism - Xu_2008_J.Mol.Biol_375_708
Author(s) : Xu Y , Nakajima Y , Ito K , Zheng H , Oyama H , Heiser U , Hoffmann T , Gartner UT , Demuth HU , Yoshimoto T
Ref : Journal of Molecular Biology , 375 :708 , 2008
Abstract : A new inhibitor, H-Ala-Ile-pyrrolidin-2-yl boronic acid, was developed as an inhibitor against prolyl tripeptidyl aminopeptidase with a K(i) value of 88.1 nM. The structure of the prolyl tripeptidyl aminopeptidase complexed with the inhibitor (enzyme-inhibitor complex) was determined at 2.2 A resolution. The inhibitor was bound to the active site through a covalent bond between Ser603 and the boron atom of the inhibitor. This structure should closely mimic the structure of the reaction intermediate between the enzyme and substrate. We previously proposed that two glutamate residues, Glu205 and Glu636, are involved in the recognition of substrates. In order to clarify the function of these glutamate residues in substrate recognition, three mutant enzymes, E205A, E205Q, and E636A were generated by site-directed mutagenesis. The E205A mutant was expressed as an inclusion body. The E205Q mutant was expressed in soluble form, but no activity was detected. Here, the structures of the E636A mutant and its complex with the inhibitor were determined. The inhibitor was located at almost the same position as in the wild-type enzyme-inhibitor complex. The amino group of the inhibitor interacted with Glu205 and the main-chain carbonyl group of Gln203. In addition, a water molecule in the place of Glu636 of the wild-type enzyme interacted with the amino group of the inhibitor. This water molecule was located near the position of Glu636 in the wild-type and formed a hydrogen bond with Gln203. The k(cat)/K(M) values of the E636A mutant toward the two substrates used were smaller than those of the wild-type by two orders of magnitude. The K(i) value of our inhibitor for the E636A mutant was 48.8 microM, which was 554-fold higher than that against the wild-type enzyme. Consequently, it was concluded that Glu205 and Glu636 are significant residues for the N-terminal recognition of a substrate.
ESTHER : Xu_2008_J.Mol.Biol_375_708
PubMedSearch : Xu_2008_J.Mol.Biol_375_708
PubMedID: 18042490
Gene_locus related to this paper: porgi-q7muw6

Title : Unusual extra space at the active site and high activity for acetylated hydroxyproline of prolyl aminopeptidase from Serratia marcescens - Nakajima_2006_J.Bacteriol_188_1599
Author(s) : Nakajima Y , Ito K , Sakata M , Xu Y , Nakashima K , Matsubara F , Hatakeyama S , Yoshimoto T
Ref : Journal of Bacteriology , 188 :1599 , 2006
Abstract : The prolyl aminopeptidase complexes of Ala-TBODA [2-alanyl-5-tert-butyl-(1, 3, 4)-oxadiazole] and Sar-TBODA [2-sarcosyl-5-tert-butyl-(1, 3, 4)-oxadiazole] were analyzed by X-ray crystallography at 2.4 angstroms resolution. Frames of alanine and sarcosine residues were well superimposed on each other in the pyrrolidine ring of proline residue, suggesting that Ala and Sar are recognized as parts of this ring of proline residue by the presence of a hydrophobic proline pocket at the active site. Interestingly, there was an unusual extra space at the bottom of the hydrophobic pocket where proline residue is fixed in the prolyl aminopeptidase. Moreover, 4-acetyloxyproline-betaNA (4-acetyloxyproline beta-naphthylamide) was a better substrate than Pro-betaNA. Computer docking simulation well supports the idea that the 4-acetyloxyl group of the substrate fitted into that space. Alanine scanning mutagenesis of Phe139, Tyr149, Tyr150, Phe236, and Cys271, consisting of the hydrophobic pocket, revealed that all of these five residues are involved significantly in the formation of the hydrophobic proline pocket for the substrate. Tyr149 and Cys271 may be important for the extra space and may orient the acetyl derivative of hydroxyproline to a preferable position for hydrolysis. These findings imply that the efficient degradation of collagen fragment may be achieved through an acetylation process by the bacteria.
ESTHER : Nakajima_2006_J.Bacteriol_188_1599
PubMedSearch : Nakajima_2006_J.Bacteriol_188_1599
PubMedID: 16452443
Gene_locus related to this paper: serma-impep

Title : Crystal structure and mechanism of tripeptidyl activity of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis - Ito_2006_J.Mol.Biol_362_228
Author(s) : Ito K , Nakajima Y , Xu Y , Yamada N , Onohara Y , Ito T , Matsubara F , Kabashima T , Nakayama K , Yoshimoto T
Ref : Journal of Molecular Biology , 362 :228 , 2006
Abstract : The crystal structure of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis was determined. Prolyl tripeptidyl aminopeptidase consists of beta-propeller and catalytic domains, and a large cavity between the domains; this structure is similar to dipeptidyl aminopeptidase IV. A catalytic triad (Ser603, His710, and Asp678) was located in the catalytic domain; this triad was virtually identical to that of the enzymes belonging to the prolyl oligopeptidase family. The structure of an inactive S603A mutant enzyme complexed with a substrate was also determined. The pyrrolidine ring of the proline residue appeared to fit into a hydrophobic pocket composed of Tyr604, Val629, Trp632, Tyr635, Tyr639, Val680, and Val681. There were characteristic differences in the residues of the beta-propeller domain, and these differences were related to the substrate specificity of tripeptidyl activity. The N-terminal amino group was recognized by salt bridges, with two carboxyl groups of Glu205 and Glu206 from a helix in dipeptidyl aminopeptidase IV. In prolyl tripeptidyl aminopeptidase, however, the Glu205 (located in the loop) and Glu636 were found to carry out this function. The loop structure provides sufficient space to accommodate three N-terminal residues (Xaa-Xaa-Pro) of substrates. This is the first report of the structure and substrate recognition mechanism of tripeptidyl peptidase.
ESTHER : Ito_2006_J.Mol.Biol_362_228
PubMedSearch : Ito_2006_J.Mol.Biol_362_228
PubMedID: 16914159
Gene_locus related to this paper: porgi-q7muw6

Title : Haplotype structures of EPHX1 and their effects on the metabolism of carbamazepine-10,11-epoxide in Japanese epileptic patients - Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
Author(s) : Nakajima Y , Saito Y , Shiseki K , Fukushima-Uesaka H , Hasegawa R , Ozawa S , Sugai K , Katoh M , Saitoh O , Ohnuma T , Kawai M , Ohtsuki T , Suzuki C , Minami N , Kimura H , Goto Y , Kamatani N , Kaniwa N , Sawada J
Ref : European Journal of Clinical Pharmacology , 61 :25 , 2005
Abstract : OBJECTIVE: Microsomal epoxide hydrolase (mEH) is an enzyme that detoxifies reactive epoxides and catalyzes the biotransformation of carbamazepine-10,11-epoxide (CBZ-epoxide) to carbamazepine-10,11-diol (CBZ-diol). Utilizing single nucleotide polymorphisms (SNPs) of the EPHX1 gene encoding mEH, we identified the haplotypes of EPHX1 blocks and investigated the association between the block haplotypes and CBZ-epoxide metabolism.
METHODS: SNPs of EPHX1 were analyzed by means of polymerase chain reaction amplification and DNA sequencing using DNA extracted from the blood leukocytes of 96 Japanese epileptic patients, including 58 carbamazepine-administered patients. The plasma concentrations of CBZ and its four metabolites were determined using high-performance liquid chromatography.
RESULTS: From sequencing all 9 exons and their surrounding introns, 29 SNPs were found in EPHX1. The SNPs were separated into three blocks on the basis of linkage disequilibrium, and the block haplotype combinations (diplotypes) were assigned. Using plasma CBZ-diol/CBZ-epoxide ratios (diol/epoxide ratios) indicative of the mEH activity, the effects of the diplotypes in each EPHX1 block were analyzed on CBZ-epoxide metabolism. In block 2, the diol/epoxide ratios increased significantly depending on the number of haplotype *2 bearing Y113H (P=0.0241). In block 3, the ratios decreased depending on the number of haplotype *2 bearing H139R (P=0.0351). Also, an increasing effect of a *1 subtype, *1c, was observed on the ratio. CONCLUSION: These results show that some EPHX1 haplotypes are associated with altered CBZ-epoxide metabolism. This is the first report on the haplotype structures of EPHX1 and their potential in vivo effects.
ESTHER : Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
PubMedSearch : Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
PubMedID: 15692831

Title : Crystallization and preliminary X-ray characterization of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis - Nakajima_2005_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_61_1046
Author(s) : Nakajima Y , Ito K , Xu Y , Yamada N , Onohara Y , Ito T , Yoshimoto T
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 61 :1046 , 2005
Abstract : A recombinant form of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis has been crystallized by the hanging-drop vapour-diffusion method using potassium sodium tartrate as a precipitating agent. The crystals belong to the hexagonal space group P6(3)22, with unit-cell parameters a = b = 149.4, c = 159.7 A. The crystals are most likely to contain one subunit of a dimer in the asymmetric unit, with a VM value of 3.14 A3 Da(-1). Diffraction data were collected to 2.1 A resolution using synchrotron radiation at the BL5 station of the Photon Factory.
ESTHER : Nakajima_2005_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_61_1046
PubMedSearch : Nakajima_2005_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_61_1046
PubMedID: 16511231
Gene_locus related to this paper: porgi-q7muw6

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 : Five novel single nucleotide polymorphisms in the EPHX1 gene encoding microsomal epoxide hydrolase - Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
Author(s) : Shiseki K , Itoda M , Saito Y , Nakajima Y , Maekawa K , Kimura H , Goto Y , Saitoh O , Katoh M , Ohnuma T , Kawai M , Sugai K , Ohtsuki T , Suzuki C , Minami N , Ozawa S , Sawada J
Ref : Drug Metab Pharmacokinet , 18 :150 , 2003
Abstract : Five novel single nucleotide polymorphisms (SNPs) were found in the EPHX1 gene from 96 Japanese epileptic patients. The detected SNPs were as follows: 1) SNP, MPJ6_EX1009; GENE NAME, EPHX1 ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-CCTCACTTCAGTG/ACTGGGCTTTGCC-3'. 2) SNP, MPJ6_EX1013; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TCCGCAGCCAGGG/CAGGACGACAGCA-3'. 3) SNP, MPJ6_EX1026; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-GTTCTCCCTGGAC/TGACCTGCTGACC-3'. 4) SNP, MPJ6_EX1028; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-AGGCAGGGGGACG/AGCCAGTCTTGGG-3'. 5) SNP, MPJ6_EX1030; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TGAAAAGTGGGTG/AAGGTTCAAGTAC-3'. The frequencies were 0.016 for MPJ6_EX1028 (IVS8+54G>A) and 0.005 for the other SNPs. The SNP MPJ6_EX1013 (130G>C) results in an amino acid alteration (E44Q). The other three SNPs in the coding region, MPJ6_EX1009 (30G>A), MPJ6_EX1026 (1056C>T), and MPJ6_EX1030 (1239G>A) result in synonymous changes (V10V, D352D, and V413V, respectively).
ESTHER : Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
PubMedSearch : Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
PubMedID: 15618730
Gene_locus related to this paper: human-EPHX1

Title : Effects of physostigmine and calcium on acetylcholine efflux from the hippocampus of freely moving rats as determined by in vivo microdialysis and a radioimmunoassay - Fujii_2000_Neurosci.Lett_289_181
Author(s) : Fujii T , Harada H , Koyama T , Nakajima Y , Kawashima K
Ref : Neuroscience Letters , 289 :181 , 2000
Abstract : The effects varying the concentration of Ca2+ in perfused artificial cerebrospinal fluid ([Ca2+]csf) on basal acetylcholine (ACh) efflux from the hippocampus of freely moving rats, in the presence and absence of the cholinesterase (ChE) inhibitor physostigmine, were investigated using in vivo microdialysis and a highly specific radioimmunoassay for ACh. In the absence of physostigmine, basal ACh efflux was 3.4+/-0.7 pg/30 min (mean +/- SEM) at [Ca2+]csf = 1.26 mM. Stepwise increases in [Ca2+]csf elicited a gradual increase in ACh efflux that was significant at [Ca2+]csf = 5.04 mM. Inhibition of ChE by addition of 10 microM physostigmine to the perfusate increased the efflux of ACh to 103.2+/-21.1 pg/30 min ([Ca2+]csf = 1.26 mM), and the efflux was augmented still further by increasing [Ca2+]csf, a change that became significant at [Ca2+]csf = 3.78. These results illustrate the sensitivity of basal ACh efflux from the hippocampus to changes in the extracellular Ca2+ concentration, and suggest that a more accurate picture of hippocampal cholinergic activity is obtained by microdialysis using normal artificial cerebrospinal fluid, under physiological conditions, rather than in the presence of a ChE inhibitor.
ESTHER : Fujii_2000_Neurosci.Lett_289_181
PubMedSearch : Fujii_2000_Neurosci.Lett_289_181
PubMedID: 10961659

Title : Enhancement of hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by repeated lithium treatment in rats - Fujii_2000_Can.J.Physiol.Pharmacol_78_392
Author(s) : Fujii T , Nakai K , Nakajima Y , Kawashima K
Ref : Canadian Journal of Physiology & Pharmacology , 78 :392 , 2000
Abstract : Hippocampal cholinergic neuronal activity is reported to be regulated, at least partly, through serotonin1A (5-HT1A) receptors. Chronic lithium treatment has been shown to alter both behavioral and neurochemical responses mediated by postsynaptic 5-HT1A receptors. We investigated whether long-term lithium treatment affects central cholinergic neurotransmission through 5-HT1A receptor-mediated pathways. Changes in acetylcholine (ACh) release induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, in the rat hippocampus were measured using a microdialysis technique and a radioimmunoassay for ACh. Administration of lithium for 21 days resulted in a serum lithium concentration of 1.03 mM and caused little change in density or affinity of [3H]8-OH-DPAT binding sites in the hippocampus. The local application of 8-OH-DPAT into the hippocampus of lithium treated rats increased the ACh efflux in both the absence and the presence of physostigmine, a cholinesterase (ChE) inhibitor, in the perfusion fluid. The basal ACh efflux of lithium treated rats was not different from that of the control rats under normal conditions, but was significantly higher than that of the controls when ChE was inhibited. These results demonstrate that chronic lithium treatment increases spontaneous ACh release in the hippocampus under conditions of ChE inhibition, but not under normal conditions, and enhances cholinergic neurotransmission through 5-HT1A receptor-mediated pathways, and suggest that activation of 5-HT1A receptor function by lithium is related to the enhancement of hippocampal cholinergic neurotransmission.
ESTHER : Fujii_2000_Can.J.Physiol.Pharmacol_78_392
PubMedSearch : Fujii_2000_Can.J.Physiol.Pharmacol_78_392
PubMedID: 10841434

Title : Enhancement of cortical and hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by BAY x 3702 in freely moving rats - Koyama_1999_Neurosci.Lett_265_33
Author(s) : Koyama T , Nakajima Y , Fujii T , Kawashima K
Ref : Neuroscience Letters , 265 :33 , 1999
Abstract : Involvement of serotonin (5-HT) in the regulation of cholinergic neuronal activity by modulation of acetylcholine (ACh) release has been reported for various regions of the brain. Cortical and hippocampal cholinergic neurotransmission is of particular importance in the mechanisms of attention as well as learning and memory. In the present study, we investigated the effect of R-(-)-2-[4-[(chroman-2-yl-methyl)-amino-butyl]-1,1-dioxo-benzo[d]++ +isothiazolone hydrochloride (BAY x 3702), a novel, high-affinity 5-HT1A receptor agonist, on ACh release in the cerebral cortex and hippocampus of freely moving rats using an in vivo microdialysis technique. Acetylcholine efflux from the cortex and hippocampus was measured every 30 m using a sensitive and specific radioimmunoassay and was stable for at least 5 h. The ACh efflux from the cortex and hippocampus was increased significantly by BAY x 3702 (0.3 mg/kg, i.p.) compared with saline administration. WAY-100635 (0.6 mg/kg, s.c.), a selective 5-HT1A receptor antagonist, eliminated the augmentation of ACh efflux induced by BAY x 3702 in both brain regions. These results demonstrate that stimulation by BAY x 3702 enhanced ACh release in both the cortex and hippocampus through 5-HT1A receptor-mediated pathways.
ESTHER : Koyama_1999_Neurosci.Lett_265_33
PubMedSearch : Koyama_1999_Neurosci.Lett_265_33
PubMedID: 10327199

Title : Cloning and characterization of ethanol-regulated esterase genes in Acetobacter pasteurianus - Kashima_1999_J.Biosci.Bioeng_87_19
Author(s) : Kashima Y , Nakajima Y , Nakano T , Tayama K , Koizumi Y , Udaka S , Yanagida F
Ref : J Biosci Bioeng , 87 :19 , 1999
Abstract : The esterase encoding genes, est1 and est2, were cloned from Acetobacter pasteurianus. Nucleotide sequence analysis of est1 revealed a gene of 954 bp, and est1 coded for an arylesterase with a molecular weight of 34863 Da consisting of 317 amino acids. The est2 gene contained an open reading frame composed of 1221 bp encoding an esterase with a molecular weight of 43389 Da consisting of 406 amino acids. The est1 gene showed some similarity, but the est2 gene showed no significant homology to other esterases reported in various microorganisms. Northern blot analysis of total RNA from A. pasteurianus revealed that transcription of the est1 gene was induced only when the cells were grown in a medium containing ethanol, and suggested that the est1 transcript is monocistronic. In contrast, transcription of the est2 gene was repressed in the presence of ethanol. In the absence of ethanol, expression of the est2-mRNA, capable of encoding a multiple number of proteins, was revealed by Northern blot analysis. In addition, deletion analysis indicated that the 5'-region of the est2 gene contained a cis-acting domain for est2 transcriptional regulation. Analysis of the est1 promoter using the chloramphenicol acetyltransferase gene as a reporter gene showed that the promoter within the 305-bp fragment upstream of the ATG initiation codon was responsible for the transcription in cells grown in the presence of ethanol. Primer extension analysis of est1-mRNA showed that the transcription initiation site was 49 bp upstream from the ATG initiation codon. The results of a gel mobility shift assay indicated that there is a regulatory protein related to est1 regulation, which may have some relation to the ethanol resistance of Acetobacter sp.
ESTHER : Kashima_1999_J.Biosci.Bioeng_87_19
PubMedSearch : Kashima_1999_J.Biosci.Bioeng_87_19
PubMedID: 16232420
Gene_locus related to this paper: acepa-aryla , acepa-este2

Title : Cultured neurons infected with an HSV-1-derived vector remain electrically excitable and responsive to neurotransmitter - Farkas_1994_Neurosci.Lett_165_153
Author(s) : Farkas RH , Nakajima S , Nakajima Y
Ref : Neuroscience Letters , 165 :153 , 1994
Abstract : Vectors derived from herpes simplex virus type 1 (HSV-1) have allowed foreign genes to be expressed in differentiated postmitotic neurons, but the usefulness of these infected neurons for electrophysiological studies has not been examined. Using a latent, non-pathogenic recombinant HSV-1 virus, we expressed E. coli beta-galactosidase in identified rat cholinergic and dopaminergic neurons in culture. The electrophysiological properties of the infected cholinergic neurons were examined. The neurons remained electrically excitable and responsive to neurotransmitter.
ESTHER : Farkas_1994_Neurosci.Lett_165_153
PubMedSearch : Farkas_1994_Neurosci.Lett_165_153
PubMedID: 7912415

Title : Freeze-fracture study of the crayfish stretch receptor - Tao-Cheng_1981_J.Comp.Neurol_200_23
Author(s) : Tao-Cheng JH , Hirosawa K , Nakajima Y , Peng HB
Ref : Journal of Comparative Neurology , 200 :23 , 1981
Abstract : The crayfish slow-adapting stretch receptor was fixed under relaxed or stretched conditions (twice the relaxed length) and then processed for freeze-fracture study. The sensory neuron membrane had evenly distributed intramembrane particles mostly on its P face. The density of these particles was higher in the cell body than in the dendritic tips, which are the terminal portions of the dendrites. The dendritic tips were cylindrical under the relaxed condition and showed deformations with stretch stimuli. When they were fixed under the stretched condition with 1.6% glutaraldehyde in 0.12 M phosphate buffer (the total osmolarity of this fixative is isosmotic with the physiological solution), the dendritic tips showed regional swelling and shrinkage. The intramembrane particle density of the swollen parts decreased and there were particle-free patches of membrane, whereas the particle density of the shrunken parts increased. On the other hand when the receptor was fixed with 1.6% glutaraldehyde in 0.2 M phosphate buffer (the total osmolarity is hyperosmotic but buffer osmolarity is isosmotic), the diameter of the dendritic tips became smaller, and their membrane particle densities were almost the same as that under the relaxed condition. The sheath cells covering the sensory neuron were characterized by their sheet-like profiles, gap junctions, and crater-like protrusions. The receptor muscle membrane had longitudinal foldings, occasional invaginations, peripheral couplings, string-shaped particle aggregates, and band-shaped particle aggregates.
ESTHER : Tao-Cheng_1981_J.Comp.Neurol_200_23
PubMedSearch : Tao-Cheng_1981_J.Comp.Neurol_200_23
PubMedID: 7251944

Title : Development of the postsynaptic membrane in Xenopus neuromuscular cultures observed by freeze-fracture and thin-section electron microscopy - Peng_1980_Brain.Res_196_11
Author(s) : Peng HB , Nakajima Y , Bridgman PC
Ref : Brain Research , 196 :11 , 1980
Abstract : The formation of synapses between cultured neurons and muscle cells from Xenopus embryos has been studied with freeze-fracture and thin-section techniques. Clusters of large P-face intramembranous particles (about 11-12 nm) were observed in both innervated and non-innervated muscle cells. They presumably represented clusters of acetylcholine (ACh) receptors because of their close resemblance to the post-junctional particle clusters at the adult neuromuscular (N-M) junctions. In one-day cocultures, particle aggregates could be observed in more than 50% of the N-M contacts. At this stage, these aggregates were diffusely distributed along the contacts. After two days of coculture, extensive and tight clustering of large particles was seen along the length of persisting N-M contacts. Each particle cluster was composed of many particle aggregates and a particle-free groove demarcated each aggregate from its neighbor, thus producing a convoluted appearance of the membrane, which corresponded well with the thin-section image of the membrane profiles at the N-M contacts. In both freeze-fracture and thin-section images, membrane depressions with a diameter of about 0.1 micron were often observed in the vicinity of N-M contacts in newly innervated muscle cells. Within the pits of these depressions a small aggregate of large particles similar to those in the sarcolemma was often encountered. Such particle-rich membrane depressions were also observed in non-innervated muscle cells. They may represent sites for the incorporation of new ACh receptors in light of current theories. Particle aggregates were also closely associated with certain deep membrane invaginations, suggesting that these structures may be involved in the concentration of ACh receptors. Close membrane contacts were observed between nerve endings and muscle cells in young cocultures thin-sectioned. Gap junction-like particle aggregates were also observed in the muscle membrane along identified young N-M contacts. These data suggest that the formation of transient gap junctions may accompany the initial stages of synaptogenesis in Xenopus N-M cultures.
ESTHER : Peng_1980_Brain.Res_196_11
PubMedSearch : Peng_1980_Brain.Res_196_11
PubMedID: 7397516

Title : A fast development of presynaptic function and structure of the neuromuscular junction in Xenopus tissue culture -
Author(s) : Peng HB , Bridgman PC , Nakajima S , Greenberg A , Nakajima Y
Ref : Brain Research , 167 :379 , 1979
PubMedID: 445134

Title : Membrane particle aggregates in innervated and noninnervated cultures of Xenopus embryonic muscle cells - Peng_1978_Proc.Natl.Acad.Sci.U.S.A_75_500
Author(s) : Peng HB , Nakajima Y
Ref : Proc Natl Acad Sci U S A , 75 :500 , 1978
Abstract : Clusters of membrane particle aggregates were found in the cultures of Xenopus embryonic muscle cells. In innervated cultures, the aggregates were usually found in the vicinity of the nerve. In terms of particle density and morphology, they resembled the postsynaptic particle aggregates of adult skeletal muscle fibers, suggesting that they may be related to acetylcholine receptors. Similar particle aggregates were also found in noninnervated cultures. They may correspond to extrajunctional clusters of acetylcholine receptors or "hot spots."
ESTHER : Peng_1978_Proc.Natl.Acad.Sci.U.S.A_75_500
PubMedSearch : Peng_1978_Proc.Natl.Acad.Sci.U.S.A_75_500
PubMedID: 272667