Nagai Y

References (16)

Title : Design, Synthesis, and Evaluation of (4 R)-1-{3-[2-((18)F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbo nyl)piperazin-1-yl]pyrrolidin-2-one ([(18)F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase - Hattori_2019_J.Med.Chem_62_2362
Author(s) : Hattori Y , Aoyama K , Maeda J , Arimura N , Takahashi Y , Sasaki M , Fujinaga M , Seki C , Nagai Y , Kawamura K , Yamasaki T , Zhang MR , Higuchi M , Koike T
Ref : Journal of Medicinal Chemistry , 62 :2362 , 2019
Abstract : Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL. By tailoring the lipophilicity of the molecule to optimize nonspecific binding and blood-brain barrier permeability, we successfully identified two compounds that show high uptake to regions enriched with MAGL. PET imaging of wild-type and MAGL-deficient mice as well as a macaque monkey indicated that [(18)F]5 ((4 R)-1-{3-[2-((18)F)fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbo nyl)piperazin-1-yl]pyrrolidin-2-one, [(18)F]T-401) specifically binds to MAGL with adequate reversibility, yielding a high contrast for MAGL within an appropriate imaging time.
ESTHER : Hattori_2019_J.Med.Chem_62_2362
PubMedSearch : Hattori_2019_J.Med.Chem_62_2362
PubMedID: 30753069
Gene_locus related to this paper: human-MGLL

Title : In Vitro and in Vivo Evaluation of (11)C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies - Cheng_2018_J.Med.Chem_61_2278
Author(s) : Cheng R , Mori W , Ma L , Alhouayek M , Hatori A , Zhang Y , Ogasawara D , Yuan G , Chen Z , Zhang X , Shi H , Yamasaki T , Xie L , Kumata K , Fujinaga M , Nagai Y , Minamimoto T , Svensson M , Wang L , Du Y , Ondrechen MJ , Vasdev N , Cravatt BF , Fowler C , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 61 :2278 , 2018
Abstract : Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including (11)C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [(11)C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.
ESTHER : Cheng_2018_J.Med.Chem_61_2278
PubMedSearch : Cheng_2018_J.Med.Chem_61_2278
PubMedID: 29481079

Title : Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin - Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
Author(s) : Thussagunpanit J , Nagai Y , Nagae M , Mashiguchi K , Mitsuda N , Ohme-Takagi M , Nakano T , Nakamura H , Asami T
Ref : Biosci Biotechnol Biochem , 81 :292 , 2017
Abstract : Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR1, a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.
ESTHER : Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
PubMedSearch : Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
PubMedID: 27858514

Title : Effect of radiolabeled metabolite elimination from the brain on the accuracy of cerebral enzyme activity estimation using positron emission tomography with substrate tracers - Ohya_2011_Neuroimage_56_1105
Author(s) : Ohya T , Okamura T , Nagai Y , Fukushi K , Irie T , Suhara T , Zhang MR , Fukumura T , Kikuchi T
Ref : Neuroimage , 56 :1105 , 2011
Abstract : Cerebral enzyme activity can be quantified using positron emission tomography (PET) in conjunction with a radiolabeled enzyme substrate. We investigated the relationship between the elimination rate (k(el)) of tracer metabolites from the brain and the precision of target enzyme activity estimation (k(3)). An initial simulation study indicated that the precision of k(3) estimates was highly dependent on k(el), and was characterized by several kinetic parameters including the ratio of k(el) and the efflux rate (k(2)) of authentic tracer (beta identical withk(el)/k(2)). The optimal tracer condition for high sensitivity was found to be beta<0.1. To verify the simulation results, we performed a PET study with a single monkey using two PET tracers, N-[(18)F]fluoroethylpiperidin-4-ylmethyl acetate ([(18)F]FEP-4MA) and N-[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A). Both of these substrate type tracers were developed for measuring cerebral acetylcholinesterase activity. There was good retention of the radioactive metabolite of [(11)C]MP4A in the brain (k(el)=0.0036+/-0.0013 min(-1), beta=0.028), whereas that of [(18)F]FEP-4MA was eliminated from the brain (k(el)=0.012+/-0.0010 min(-1), beta=0.085). A non-linear least square analysis for simultaneous estimation of all parameters showed that the precision of the k(3) estimate for [(18)F]FEP-4MA was as high (7.4%) as that for [(11)C]MP4A (10%). These results indicate that tracers with metabolites that are eliminated from the brain at a slow rate (beta<0.1) may be useful for the quantitative measurement of target enzyme activity.
ESTHER : Ohya_2011_Neuroimage_56_1105
PubMedSearch : Ohya_2011_Neuroimage_56_1105
PubMedID: 21324368

Title : Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination - Nagai_2010_J.Biol.Chem_285_11114
Author(s) : Nagai Y , Nishimura A , Tago K , Mizuno N , Itoh H
Ref : Journal of Biological Chemistry , 285 :11114 , 2010
Abstract : The alpha subunit of stimulatory G protein (G alpha(s)) activates adenylyl cyclase, which catalyzes cAMP production, and regulates many physiological aspects, such as cardiac regulation and endocrine systems. Ric-8B (resistance to inhibitors of cholinesterase 8B) has been identified as the G alpha(s)-binding protein; however, its role in G(s) signaling remains obscure. In this study, we present evidence that Ric-8B specifically and positively regulates G(s) signaling by stabilizing the G alpha(s) protein. An in vitro biochemical study suggested that Ric-8B does not possess guanine nucleotide exchange factor activity. However, knockdown of Ric-8B attenuated beta-adrenergic agonist-induced cAMP accumulation, indicating that Ric-8B positively regulates G(s) signaling. Interestingly, overexpression and knockdown of Ric-8B resulted in an increase and a decrease in the G alpha(s) protein, respectively, without affecting the G alpha(s) mRNA level. We found that the G alpha(s) protein is ubiquitinated and that this ubiquitination is inhibited by Ric-8B. This Ric-8B-mediated inhibition of G alpha(s) ubiquitination requires interaction between Ric-8B and G alpha(s) because Ric-8B splicing variants, which are defective for G alpha(s) binding, failed to inhibit the ubiquitination. Taken together, these results suggest that Ric-8B plays a critical and specific role in the control of G alpha(s) protein levels by modulating G alpha(s) ubiquitination and positively regulates G(s) signaling.
ESTHER : Nagai_2010_J.Biol.Chem_285_11114
PubMedSearch : Nagai_2010_J.Biol.Chem_285_11114
PubMedID: 20133939

Title : Genome and virulence determinants of high virulence community-acquired MRSA - Baba_2002_Lancet_359_1819
Author(s) : Baba T , Takeuchi F , Kuroda M , Yuzawa H , Aoki K , Oguchi A , Nagai Y , Iwama N , Asano K , Naimi T , Kuroda H , Cui L , Yamamoto K , Hiramatsu K
Ref : Lancet , 359 :1819 , 2002
Abstract : BACKGROUND: A new type of meticillin-resistant Staphylococcus aureus (MRSA), designated community-acquired MRSA, is becoming increasingly noticeable in the community, some strains of which cause fatal infections in otherwise healthy individuals. By contrast with hospital-acquired MRSA, community-acquired MRSA is more susceptible to non b-lactam antibiotics. We investigated the high virulence potential of certain strains of this bacterium.
METHODS: We ascertained the whole genome sequence of MW2, a strain of community-acquired MRSA, by shotgun cloning and sequencing. MW2 caused fatal septicaemia and septic arthritis in a 16-month-old girl in North Dakota, USA, in 1998. The genome of this strain was compared with those of hospital-acquired MRSA strains, including N315 and Mu50. FINDINGS: Meticillin resistance gene (mecA) in MW2 was carried by a novel allelic form (type IVa) of staphylococcal cassette chromosome mec (SCCmec), by contrast with type II in N315 and Mu50. Type IVa SCCmec did not carry any of the multiple antibiotic resistance genes reported in type II SCCmec. By contrast, 19 additional virulence genes were recorded in the MW2 genome. All but two of these virulence genes were noted in four of the seven genomic islands of MW2. INTERPRETATION: MW2 carried a range of virulence and resistance genes that was distinct from those displayed on the chromosomes of extant S aureus strains. Most genes were carried by specific allelic forms of genomic islands in the MW2 chromosome. The combination of allelic forms of genomic islands is the genetic basis that determines the pathogenicity of medically important phenotypes of S aureus, including those of community-acquired MRSA strains.
ESTHER : Baba_2002_Lancet_359_1819
PubMedSearch : Baba_2002_Lancet_359_1819
PubMedID: 12044378
Gene_locus related to this paper: staau-d2uin3 , staau-LIP , staau-lipas , staau-MW0741 , staau-MW2456 , staau-q6gfm6 , staau-SA0011 , staau-SA0569 , staau-SA0572 , staau-SA0897 , staau-SA1143 , staau-SA2240 , staau-SA2306 , staau-SA2367 , staau-SA2422 , staau-SAV0321 , staau-SAV0446 , staau-SAV0457 , staau-SAV0655 , staau-SAV1014 , staau-SAV1765 , staau-SAV1793 , staau-SAV2188 , staau-SAV2350

Title : A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid - Sonoda_2002_J.Biol.Chem_277_34254
Author(s) : Sonoda H , Aoki J , Hiramatsu T , Ishida M , Bandoh K , Nagai Y , Taguchi R , Inoue K , Arai H
Ref : Journal of Biological Chemistry , 277 :34254 , 2002
Abstract : Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological properties, although its synthetic pathways have not been completely solved. We report the cloning and characterization of a novel phosphatidic acid (PA)-selective phospholipase A(1) (PLA(1)) that produces 2-acyl-LPA. The PLA(1) was identified in the GenBank(TM) data base as a close homologue of phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)). When expressed in insect Sf9 cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did not show any catalytic activity toward exogenously added phospholipid substrates. However, culture medium obtained from Sf9 cells expressing the enzyme was found to activate EDG7/LPA(3), a cellular receptor for 2-acyl-LPA. The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process. In the latter condition, an increased level of LPA, but not other lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the enzyme is observed in several human tissues such as prostate, testis, ovary, pancreas, and especially platelets. These data show that the enzyme is a membrane-associated PA-selective PLA(1) and suggest that it has a role in LPA production.
ESTHER : Sonoda_2002_J.Biol.Chem_277_34254
PubMedSearch : Sonoda_2002_J.Biol.Chem_277_34254
PubMedID: 12063250
Gene_locus related to this paper: human-LIPH

Title : Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 - Kawarabayasi_2001_DNA.Res_8_123
Author(s) : Kawarabayasi Y , Hino Y , Horikawa H , Jin-no K , Takahashi M , Sekine M , Baba S , Ankai A , Kosugi H , Hosoyama A , Fukui S , Nagai Y , Nishijima K , Otsuka R , Nakazawa H , Takamiya M , Kato Y , Yoshizawa T , Tanaka T , Kudoh Y , Yamazaki J , Kushida N , Oguchi A , Aoki K , Masuda S , Yanagii M , Nishimura M , Yamagishi A , Oshima T , Kikuchi H
Ref : DNA Research , 8 :123 , 2001
Abstract : The complete genomic sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 which optimally grows at 80 degrees C, at low pH, and under aerobic conditions, has been determined by the whole genome shotgun method with slight modifications. The genomic size was 2,694,756 bp long and the G + C content was 32.8%. The following RNA-coding genes were identified: a single 16S-23S rRNA cluster, one 5S rRNA gene and 46 tRNA genes (including 24 intron-containing tRNA genes). The repetitive sequences identified were SR-type repetitive sequences, long dispersed-type repetitive sequences and Tn-like repetitive elements. The genome contained 2826 potential protein-coding regions (open reading frames, ORFs). By similarity search against public databases, 911 (32.2%) ORFs were related to functional assigned genes, 921 (32.6%) were related to conserved ORFs of unknown function, 145 (5.1%) contained some motifs, and remaining 849 (30.0%) did not show any significant similarity to the registered sequences. The ORFs with functional assignments included the candidate genes involved in sulfide metabolism, the TCA cycle and the respiratory chain. Sequence comparison provided evidence suggesting the integration of plasmid, rearrangement of genomic structure, and duplication of genomic regions that may be responsible for the larger genomic size of the S. tokodaii strain7 genome. The genome contained eukaryote-type genes which were not identified in other archaea and lacked the CCA sequence in the tRNA genes. The result suggests that this strain is closer to eukaryotes among the archaea strains so far sequenced. The data presented in this paper are also available on the internet homepage (http:\/\/\/E-home\/genome_list-e.html\/).
ESTHER : Kawarabayasi_2001_DNA.Res_8_123
PubMedSearch : Kawarabayasi_2001_DNA.Res_8_123
PubMedID: 11572479
Gene_locus related to this paper: sulto-ST0002 , sulto-ST0071 , sulto-ST0672 , sulto-ST0779 , sulto-ST1414 , sulto-ST1737 , sulto-ST1745 , sulto-ST2026 , sulto-ST2099 , sulto-ST2511

Title : Whole genome sequencing of meticillin-resistant Staphylococcus aureus - Kuroda_2001_Lancet_357_1225
Author(s) : Kuroda M , Ohta T , Uchiyama I , Baba T , Yuzawa H , Kobayashi I , Cui L , Oguchi A , Aoki K , Nagai Y , Lian J , Ito T , Kanamori M , Matsumaru H , Maruyama A , Murakami H , Hosoyama A , Mizutani-Ui Y , Takahashi NK , Sawano T , Inoue R , Kaito C , Sekimizu K , Hirakawa H , Kuhara S , Goto S , Yabuzaki J , Kanehisa M , Yamashita A , Oshima K , Furuya K , Yoshino C , Shiba T , Hattori M , Ogasawara N , Hayashi H , Hiramatsu K
Ref : Lancet , 357 :1225 , 2001
Abstract : BACKGROUND: Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism.
METHODS: Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction. FINDINGS: The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors. INTERPRETATION: The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.
ESTHER : Kuroda_2001_Lancet_357_1225
PubMedSearch : Kuroda_2001_Lancet_357_1225
PubMedID: 11418146
Gene_locus related to this paper: staau-LIP , staau-lipas , staau-MW0741 , staau-MW2456 , staau-q6gfm6 , staau-SA0011 , staau-SA0569 , staau-SA0572 , staau-SA0897 , staau-SA1143 , staau-SA2240 , staau-SA2306 , staau-SA2367 , staau-SA2422 , staau-SAV0321 , staau-SAV0446 , staau-SAV0457 , staau-SAV0655 , staau-SAV1014 , staau-SAV1765 , staau-SAV1793 , staau-SAV2188 , staau-SAV2350 , staau-SAV2484 , staau-SAV2594

Title : A 38 kb segment containing the cdc2 gene from the left arm of fission yeast chromosome II: sequence analysis and characterization of the genomic DNA and cDNAs encoded on the segment - Machida_2000_Yeast_16_71
Author(s) : Machida M , Yamazaki S , Kunihiro S , Tanaka T , Kushida N , Jinnno K , Haikawa Y , Yamazaki J , Yamamoto S , Sekine M , Oguchi A , Nagai Y , Sakai M , Aoki K , Ogura K , Kudoh Y , Kikuchi H , Zhang MQ , Yanagida M
Ref : Yeast , 16 :71 , 2000
Abstract : A genomic 38 kbp segment on the c1750 cosmid clone containing the cdc2 gene, located in the left arm of chromosome II from Schizosaccharomyces pombe, was sequenced. The segment was found to have five previously known genes, pht1, cdc2, his3, act1 and mei4. Among 11 coding sequences (CDSs) predicted by the gene finding software INTRON.PLOT., four CDSs, pi007, pi010, pi014 and pi016, had considerable similarity to 40S ribosomal protein, glycosyltransferase, cdc2-related protein kinase and alpha-1, 2-mannosyltransferase, respectively. Another unusually huge open reading frame (ORF) (pi011), consisting of 2233 amino acids, existed, having significant homology to alpha-amylase, granule-bound glycogen synthase and the Sz. pombe YS 1110 clone product at the N-terminal, middle and C-terminal regions, respectively. All the predicted 11 CDSs were experimentally analysed by RACE PCR. The sequencing of the RACE products revealed that there were two small overlaps at the 3' untranslated regions (UTRs) between pi004 and pi005 (17 bp) and between pi007 and pi008 (2 bp). The distances between 5' end of the 5'UTR and the putative translation initiation codon varied from 10 to 302 nucleotides (nt) among the nine CDSs successfully analysed by 5'-RACE. The expression level of each CDS on this clone was determined. Among the 16 genes on this clone, the previously determined genes, pht1, cdc2, his3 and act1, were found to be most highly expressed. Finally, cDNAs of all the newly identified genes were detected by RACE, proving the actual expression of these genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AB004534.
ESTHER : Machida_2000_Yeast_16_71
PubMedSearch : Machida_2000_Yeast_16_71
PubMedID: 10620777
Gene_locus related to this paper: schpo-be46

Title : An alternative splicing form of phosphatidylserine-specific phospholipase A1 that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans - Nagai_1999_J.Biol.Chem_274_11053
Author(s) : Nagai Y , Aoki J , Sato T , Amano K , Matsuda Y , Arai H and
Ref : Journal of Biological Chemistry , 274 :11053 , 1999
Abstract : Phosphatidylserine-specific phospholipase A1 (PS-PLA1), which acts specifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to hydrolyze fatty acids at the sn-1 position of these phospholipids, was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In this study we isolated and sequenced cDNA clones encoding human PS-PLA1, which showed 80% homology with rat PS-PLA1 at the amino acid level. In addition to an mRNA encoding a 456-amino acid product (PS-PLA1), an mRNA with four extra bases inserted at the boundary of the exon-intron junction was detected in human tissues and various human cell lines. This mRNA is most probably produced via an alternative use of the 5'-splicing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS-PLA1DeltaC) that lacks two-thirds of the C-terminal domain of PS-PLA1. Unlike PS-PLA1, PS-PLA1DeltaC hydrolyzed exclusively lyso-PS but not PS appreciably. Any other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives were not hydrolyzed at all. These data demonstrated that PS-PLA1DeltaC exhibits lyso-PS-specific lysophospholipase activity and that the C-terminal domain of PS-PLA1 is responsible for recognizing diacylphospholipids. In addition, human PS-PLA1 gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).
ESTHER : Nagai_1999_J.Biol.Chem_274_11053
PubMedSearch : Nagai_1999_J.Biol.Chem_274_11053
PubMedID: 10196188
Gene_locus related to this paper: human-PLA1A

Title : Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1 - Kawarabayasi_1999_DNA.Res_6_83
Author(s) : Kawarabayasi Y , Hino Y , Horikawa H , Yamazaki S , Haikawa Y , Jin-no K , Takahashi M , Sekine M , Baba S , Ankai A , Kosugi H , Hosoyama A , Fukui S , Nagai Y , Nishijima K , Nakazawa H , Takamiya M , Masuda S , Funahashi T , Tanaka T , Kudoh Y , Yamazaki J , Kushida N , Oguchi A , Aoki KI , Kubota K , Nakamura Y , Nomura N , Sako Y , Kikuchi H
Ref : DNA Research , 6 :83 , 1999
Abstract : The complete sequence of the genome of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1, which optimally grows at 95 degrees C, has been determined by the whole genome shotgun method with some modifications. The entire length of the genome was 1,669,695 bp. The authenticity of the entire sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2,694 open reading frames (ORFs) were assigned. By similarity search against public databases, 633 (23.5%) of the ORFs were related to genes with putative function and 523 (19.4%) to the sequences registered but with unknown function. All the genes in the TCA cycle except for that of alpha-ketoglutarate dehydrogenase were included, and instead of the alpha-ketoglutarate dehydrogenase gene, the genes coding for the two subunits of 2-oxoacid:ferredoxin oxidoreductase were identified. The remaining 1,538 ORFs (57.1%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs suggested that a considerable member of ORFs were generated by sequence duplication. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 47 tRNA genes including 14 genes with intron structures. All the assigned ORFs and RNA coding regions occupied 89.12% of the whole genome. The data presented in this paper are available on the internet homepage (http:\/\/
ESTHER : Kawarabayasi_1999_DNA.Res_6_83
PubMedSearch : Kawarabayasi_1999_DNA.Res_6_83
PubMedID: 10382966
Gene_locus related to this paper: aerpe-APE1244 , aerpe-APE1547 , aerpe-APE1832 , aerpe-APE2290 , aerpe-APE2361 , aerpe-APE2441

Title : Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat - Matsui_1999_Drug.Metab.Dispos_27_1406
Author(s) : Matsui K , Mishima M , Nagai Y , Yuzuriha T , Yoshimura T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 27 :1406 , 1999
Abstract : Donepezil hydrochloride (Aricept) is a drug for the treatment of Alzheimer's disease. The absorption, distribution, metabolism, and excretion of donepezil were investigated in male Sprague-Dawley rats after a single oral administration. Orally administered (14)C-labeled donepezil was absorbed rapidly. The plasma level of unchanged donepezil declined more rapidly than that of radioactivity, and the brain level of radioactivity declined almost in parallel with the plasma level of unchanged donepezil. The ratio of donepezil to total radioactivity in brain was 86.9 to 93.0%, indicating low permeability of the metabolites through the blood-brain barrier. No heterogeneous localization of radioactivity was recognized in the brain and the concentration in each part of the brain was 1.74 to 2.24 times the plasma concentration. Cumulative biliary, urinary, and fecal excretion of radioactivity in bile duct-cannulated rats was 72.9, 24.4, and 8.84%, respectively, of the administered radioactivity at 48 h after administration. These results indicate that the absorption of donepezil is almost complete, and that its metabolites are mainly excreted into feces through the bile and some of them are subject to enterohepatic circulation. The metabolism of donepezil was extensive in rats and involved O-demethylation, aromatic hydroxylation, N-dealkylation, N-oxidation, and glucuronide conjugation of O-demethylate. The structures of the metabolites were determined by mass spectrometry and (1)H-NMR analysis. In plasma, urine, and bile, O-glucuronides accounted for the majority of the radioactivity, and in brain, unchanged donepezil was mostly detected. No metabolites were found in brain. There was no notable accumulation of radioactivity in whole blood and tissues.
ESTHER : Matsui_1999_Drug.Metab.Dispos_27_1406
PubMedSearch : Matsui_1999_Drug.Metab.Dispos_27_1406
PubMedID: 10570021

Title : Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3 - Kawarabayasi_1998_DNA.Res_5_55
Author(s) : Kawarabayasi Y , Sawada M , Horikawa H , Haikawa Y , Hino Y , Yamamoto S , Sekine M , Baba S , Kosugi H , Hosoyama A , Nagai Y , Sakai M , Ogura K , Otsuka R , Nakazawa H , Takamiya M , Ohfuku Y , Funahashi T , Tanaka T , Kudoh Y , Yamazaki J , Kushida N , Oguchi A , Aoki K , Kikuchi H
Ref : DNA Research , 5 :55 , 1998
Abstract : The complete sequence of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3, has been determined by assembling the sequences of the physical map-based contigs of fosmid clones and of long polymerase chain reaction (PCR) products which were used for gap-filling. The entire length of the genome was 1,738,505 bp. The authenticity of the entire genome sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2061 open reading frames (ORFs) were assigned, and by similarity search against public databases, 406 (19.7%) were related to genes with putative function and 453 (22.0%) to the sequences registered but with unknown function. The remaining 1202 ORFs (58.3%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs in the genome provided evidence that a considerable number of ORFs were generated by sequence duplication. By similarity search, 11 ORFs were assumed to contain the intein elements. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 46 tRNA genes including two with the intron structure. All the assigned ORFs and RNA coding regions occupied 91.25% of the whole genome. The data presented in this paper are available on the internet at
ESTHER : Kawarabayasi_1998_DNA.Res_5_55
PubMedSearch : Kawarabayasi_1998_DNA.Res_5_55
PubMedID: 9679194
Gene_locus related to this paper: pyrho-PH0594 , pyrho-PH0863 , pyrho-PH1262

Title : Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family - Sato_1997_J.Biol.Chem_272_2192
Author(s) : Sato T , Aoki J , Nagai Y , Dohmae N , Takio K , Doi T , Arai H , Inoue K
Ref : Journal of Biological Chemistry , 272 :2192 , 1997
Abstract : Rat platelets secrete two types of phospholipases upon stimulation; one is type II phospholipase A2 and the other is serine-phospholipid-selective phospholipase A. In the current study we purified serine-phospholipid-selective phospholipase A and cloned its cDNA. The final preparation, purified from extracellular medium of activated rat platelets, gave a 55-kDa protein band on SDS-polyacrylamide gel electrophoresis. [3H]Diisopropyl fluorophosphate, an inhibitor of the enzyme, labeled the 55-kDa protein, suggesting that this polypeptide possesses active serine residues. The cDNA for the enzyme was cloned from a rat megakaryocyte cDNA library. The predicted 456-amino acid sequence contains a putative short N-terminal signal sequence and a GXSXG sequence, which is a motif of an active serine residue of serine esterase. Amino acid sequence homology analysis revealed that the enzyme shares about 30% homology with mammalian lipases (lipoprotein lipase, hepatic lipase, and pancreatic lipase). Regions surrounding the putative active serine, histidine, and aspartic acid, which may form a "lipase triad," were highly conserved among these enzymes. The recombinant protein, which we expressed in Sf9 insect cells using the baculovirus system, hydrolyzed a fatty acyl residue at the sn-1 position of lysophosphatidylserine and phosphatidylserine, but did not appreciably hydrolyze phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, and triglyceride. The present enzyme, named phosphatidylserine-phospholipase A1, is the first phospholipase that exclusively hydrolyses the sn-1 position and has a strict head group specificity for the substrate.
ESTHER : Sato_1997_J.Biol.Chem_272_2192
PubMedSearch : Sato_1997_J.Biol.Chem_272_2192
PubMedID: 8999922
Gene_locus related to this paper: human-PLA1A , ratno-P97535

Title : Effect of TAK-147, a novel AChE inhibitor, on cerebral energy metabolism - Nakayama_1996_Neurobiol.Aging_17_849
Author(s) : Nakayama T , Takahashi H , Miyamoto M , Goto G , Nagai Y
Ref : Neurobiology of Aging , 17 :849 , 1996
Abstract : Effect of TAK-147, a novel acetylcholinesterase (AChE) inhibitor, on cerebral energy metabolism was investigated using an in vivo 31P-magnetic resonance spectroscopy (31P-MRS) technique and the autoradiographic 2-deoxy-[14C]-D-glucose method in aged Fischer 344 rats. We revealed that high-energy phosphate metabolites, phosphocreatine (PCr) and ATP, in the brain decreased gradually with aging and that significant decrement of cerebral PCr and ATP was observed from 13- and 8.5-month-old in comparison with those of 2.5-month-old rats, respectively. Daily oral administration of TAK-147 (1 mg/kg) for 40 days increased PCr and ATP levels in aged rats (29-month-old). To determine the site at which TAK-147 acts to increase high-energy phosphate metabolism, we investigated the rate of local cerebral glucose utilization (LCGU) in various brain regions. The rate of LCGU decreased in almost all brain regions in aged rats (28 months of age), and the decrease was significant in 29 out of the 35 regions. When TAK-147 was administered orally to the aged rats, the levels were dose dependently increased, especially in the auditory cortex. These results indicate that TAK-147 increases cerebral energy metabolism in aged rats.
ESTHER : Nakayama_1996_Neurobiol.Aging_17_849
PubMedSearch : Nakayama_1996_Neurobiol.Aging_17_849
PubMedID: 9363795