Hasegawa Y

References (10)

Title : ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue - Galmozzi_2014_Cell.Rep_9_1584
Author(s) : Galmozzi A , Sonne SB , Altshuler-Keylin S , Hasegawa Y , Shinoda K , Luijten IH , Chang JW , Sharp LZ , Cravatt BF , Saez E , Kajimura S
Ref : Cell Rep , 9 :1584 , 2014
Abstract : Obesity develops when energy intake chronically exceeds energy expenditure. Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications. The ability of BAT to dissipate energy is dependent on expression of mitochondrial uncoupling protein 1 (UCP1). To facilitate the identification of pharmacological modulators of BAT UCP1 levels, which may have potential as antiobesity medications, we developed a transgenic model in which luciferase activity faithfully mimics endogenous UCP1 expression and its response to physiologic stimuli. Phenotypic screening of a library using cells derived from this model yielded a small molecule that increases UCP1 expression in brown fat cells and mice. Upon adrenergic stimulation, compound-treated mice showed increased energy expenditure. These tools offer an opportunity to identify pharmacologic modulators of UCP1 expression and uncover regulatory pathways that impact BAT-mediated thermogenesis.
ESTHER : Galmozzi_2014_Cell.Rep_9_1584
PubMedSearch : Galmozzi_2014_Cell.Rep_9_1584
PubMedID: 25466254

Title : Characterization of CpdC, a large-ring lactone-hydrolyzing enzyme from Pseudomonas sp. strain HI-70, and its use as a fusion tag facilitating overproduction of proteins in Escherichia coli - Xu_2013_Appl.Environ.Microbiol_79_7091
Author(s) : Xu Y , Grosse S , Iwaki H , Hasegawa Y , Lau PC
Ref : Applied Environmental Microbiology , 79 :7091 , 2013
Abstract : There are few entries of carbon-carbon bond hydrolases (EC 3.7.1.-) in the ExPASy database. In microbes, these enzymes play an essential role in the metabolism of alicyclic or aromatic compounds as part of the global carbon cycle. CpdC is a omega-pentadecalactone hydrolase derived from the degradation pathway of cyclopentadecanol or cyclopentadecanone by Pseudomonas sp. strain HI-70. CpdC was purified to homogeneity and characterized. It is active as a dimer of 56,000 Da with a subunit molecular mass of 33,349. Although CpdC has the highest activity and reaction rate (kcat) toward omega-pentadecalactone, its catalytic efficiency favors lauryl lactone as a substrate. The melting temperature (Tm) of CpdC was estimated to be 50.9 +/- 0.1 degrees C. The half-life of CpdC at 35 degrees C is several days. By virtue of its high level of expression in Escherichia coli, the intact CpdC-encoding gene and progressive 3'-end deletions were employed in the construction of a series of fusion plasmid system. Although we found them in inclusion bodies, proof-of-concept of overproduction of three microbial cutinases of which the genes were otherwise expressed poorly or not at all in E. coli was demonstrated. On the other hand, two antigenic proteins, azurin and MPT63, were readily produced in soluble form.
ESTHER : Xu_2013_Appl.Environ.Microbiol_79_7091
PubMedSearch : Xu_2013_Appl.Environ.Microbiol_79_7091
PubMedID: 24038681

Title : Pseudomonad cyclopentadecanone monooxygenase displaying an uncommon spectrum of Baeyer-Villiger oxidations of cyclic ketones - Iwaki_2006_Appl.Environ.Microbiol_72_2707
Author(s) : Iwaki H , Wang S , Grosse S , Bergeron H , Nagahashi A , Lertvorachon J , Yang J , Konishi Y , Hasegawa Y , Lau PC
Ref : Applied Environmental Microbiology , 72 :2707 , 2006
Abstract : Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts that offer the prospect of high chemo-, regio-, and enantioselectivity in the organic synthesis of lactones or esters from a variety of ketones. In this study, we have cloned, sequenced, and overexpressed in Escherichia coli a new BVMO, cyclopentadecanone monooxygenase (CpdB or CPDMO), originally derived from Pseudomonas sp. strain HI-70. The 601-residue primary structure of CpdB revealed only 29% to 50% sequence identity to those of known BVMOs. A new sequence motif, characterized by a cluster of charged residues, was identified in a subset of BVMO sequences that contain an N-terminal extension of approximately 60 to 147 amino acids. The 64-kDa CPDMO enzyme was purified to apparent homogeneity, providing a specific activity of 3.94 micromol/min/mg protein and a 20% yield. CPDMO is monomeric and NADPH dependent and contains approximately 1 mol flavin adenine dinucleotide per mole of protein. A deletion mutant suggested the importance of the N-terminal 54 amino acids to CPDMO activity. In addition, a Ser261Ala substitution in a Rossmann fold motif resulted in an improved stability and increased affinity of the enzyme towards NADPH compared to the wild-type enzyme (K(m) = 8 microM versus K(m) = 24 microM). Substrate profiling indicated that CPDMO is unusual among known BVMOs in being able to accommodate and oxidize both large and small ring substrates that include C(11) to C(15) ketones, methyl-substituted C(5) and C(6) ketones, and bicyclic ketones, such as decalone and beta-tetralone. CPDMO has the highest affinity (K(m) = 5.8 microM) and the highest catalytic efficiency (k(cat)/K(m) ratio of 7.2 x 10(5) M(-1) s(-1)) toward cyclopentadecanone, hence the Cpd designation. A number of whole-cell biotransformations were carried out, and as a result, CPDMO was found to have an excellent enantioselectivity (E > 200) as well as 99% S-selectivity toward 2-methylcyclohexanone for the production of 7-methyl-2-oxepanone, a potentially valuable chiral building block. Although showing a modest selectivity (E = 5.8), macrolactone formation of 15-hexadecanolide from the kinetic resolution of 2-methylcyclopentadecanone using CPDMO was also demonstrated.
ESTHER : Iwaki_2006_Appl.Environ.Microbiol_72_2707
PubMedSearch : Iwaki_2006_Appl.Environ.Microbiol_72_2707
PubMedID: 16597975

Title : Irinotecan therapy in a 12-year-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity: case report - Ishikawa_2005_J.Neurooncol_74_283
Author(s) : Ishikawa K , Kajita Y , Hasegawa Y , Noda Y , Yoshida J , Nabeshima T
Ref : J Neurooncol , 74 :283 , 2005
Abstract : A 10-year-old girl was diagnosed with astrocytoma grade 2. Immuno-chemo-radiotherapy (interferon, ranimustine, and radiation), second-line chemotherapy (carboplatin and etoposide, 7 cycles) and third-line chemotherapy (ifosfamide, carboplatin, and etoposide) was given to treat progressive disease. Finally, irinotecan therapy was initiated and led to dramatic clinical improvement. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) to yield its beta-glucuronide. The polymorphic UGT isoenzyme, UGT1A1 has genetic variants which decrease in SN-38 glucuronidating capacity and could help predict irinotecan-associated toxicity. The patient suffered excessive toxicity with low-dose irinotecan although no functional polymorphism in UGT1A1 was identified. We suggest that irinotecan offers an effective treatment option for children with recurrent brain stem glioma and other genetic variants except UGT1A1 may be a risk factor for irinotecan-induced toxicity.
ESTHER : Ishikawa_2005_J.Neurooncol_74_283
PubMedSearch : Ishikawa_2005_J.Neurooncol_74_283
PubMedID: 16187025

Title : Genetic polymorphisms of the multidrug resistance-associated protein 2 gene (ABCC2) and Irinotecan toxicity - Kitagawa_2004_J.Clin.Oncol_22_2009
Author(s) : Kitagawa C , Ando M , Ando Y , Sekido Y , Usui M , Takahashi K , Shimokata K , Hasegawa Y
Ref : J Clin Oncol , 22 :2009 , 2004
Abstract : 2009 Background: Irinotecan unexpectedly causes severe, occasionally fatal, toxicity of leukopenia or diarrhea. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) 1A1 to yield its b-glucuronide. Multidrug resistance-assocciated protein 2 (MRP2, ABCC2) transports SN-38-glucuronide from hepatocytes to the bile, as it transports bilirubin in the body.
METHODS: We examined the polymorphisms of ABCC2 gene, -24C>T, 1249G>A, 2366C>T, 2302C>T, 2375A>G, 2439+2 T>C, 3449 G>A, and 3517A>T, in 120 Japanese cancer patients who had been treated with irinotecan, including 27 patients who experienced severe toxicity of G4 leukopenia and/or G3 or worse diarrhea. Our hypothesis was that patients with the variant ABCC2 allele would have an increased risk of severe toxicity.
RESULTS: We detected the four variant alleles, -24C>T, 1249G>A, 2366C>T, and 2375A>G. The association between ABCC2 variants, -24C>T or 1249G>A, and severe toxicity was investigated (Table). Neither univariate analysis (odds ratio, 0.78; 95% confidential interval (CI), 0.21-2.35; odds ratio, 1.05; 95% CI, 0.41-2.56) nor multivariate logistic regression analysis (odds ratio, 0.98; 95% CI, 0.23-3.44; odds ratio, 1.17; 95% CI, 0.40-3.26) found any significant association between severe toxicity and the ABCC2 variants in 1249G>A or -24C>T, respectively. We detected a heterozygote for 2366C>T in one patient and a new heterozygote for 2375A>G in one patient. Severe toxicity was not occurred in these patients. There were no apparent associations between the ABCC2 variants and pharmacokinetics of irinotecan, SN-38 and SN-38 glucuronide.
CONCLUSIONS: This pharmacogenetic study did not find any evidence that determination of ABCC2 genotypes would be useful for predicting severe toxicity by irinotecan. [Figure: see text] No significant financial relationships to disclose.
ESTHER : Kitagawa_2004_J.Clin.Oncol_22_2009
PubMedSearch : Kitagawa_2004_J.Clin.Oncol_22_2009
PubMedID: 28015787

Title : What influences the results in critical patients after cardiovascular surgery? - Ishikawa_2004_Asian.Cardiovasc.Thorac.Ann_12_250
Author(s) : Ishikawa S , Koyano T , Takahashi T , Sato Y , Hasegawa Y , Ohki S , Oshima K , Oki S , Kunimoto F , Morishita Y
Ref : Asian Cardiovasc Thorac Ann , 12 :250 , 2004
Abstract : The predictive factors of surgical outcome were evaluated in compromised patients following cardiovascular surgery. Of 608 patients undergoing cardiovascular surgery between 1991 and 1999, 55 stayed in the intensive care unit for 2 weeks or longer. The mean age of these 55 patients was 56 years. There were 35 survivors and 20 nonsurvivors. Postoperative respiratory failure and gastrointestinal complications were significantly more frequent in those who died. The survival rate was significantly higher in patients who had enteral feeding compared to those who did not (88% versus 43%). Serum cholinesterase and total cholesterol concentrations were higher in the survivors. It was concluded that postoperative respiratory and gastrointestinal conditions influenced the surgical outcome, and serum cholinesterase and total cholesterol concentrations were valuable predictors of survival.
ESTHER : Ishikawa_2004_Asian.Cardiovasc.Thorac.Ann_12_250
PubMedSearch : Ishikawa_2004_Asian.Cardiovasc.Thorac.Ann_12_250
PubMedID: 15353466

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp

Title : Functional annotation of a full-length mouse cDNA collection - Kawai_2001_Nature_409_685
Author(s) : Kawai J , Shinagawa A , Shibata K , Yoshino M , Itoh M , Ishii Y , Arakawa T , Hara A , Fukunishi Y , Konno H , Adachi J , Fukuda S , Aizawa K , Izawa M , Nishi K , Kiyosawa H , Kondo S , Yamanaka I , Saito T , Okazaki Y , Gojobori T , Bono H , Kasukawa T , Saito R , Kadota K , Matsuda H , Ashburner M , Batalov S , Casavant T , Fleischmann W , Gaasterland T , Gissi C , King B , Kochiwa H , Kuehl P , Lewis S , Matsuo Y , Nikaido I , Pesole G , Quackenbush J , Schriml LM , Staubli F , Suzuki R , Tomita M , Wagner L , Washio T , Sakai K , Okido T , Furuno M , Aono H , Baldarelli R , Barsh G , Blake J , Boffelli D , Bojunga N , Carninci P , de Bonaldo MF , Brownstein MJ , Bult C , Fletcher C , Fujita M , Gariboldi M , Gustincich S , Hill D , Hofmann M , Hume DA , Kamiya M , Lee NH , Lyons P , Marchionni L , Mashima J , Mazzarelli J , Mombaerts P , Nordone P , Ring B , Ringwald M , Rodriguez I , Sakamoto N , Sasaki H , Sato K , Schonbach C , Seya T , Shibata Y , Storch KF , Suzuki H , Toyo-oka K , Wang KH , Weitz C , Whittaker C , Wilming L , Wynshaw-Boris A , Yoshida K , Hasegawa Y , Kawaji H , Kohtsuki S , Hayashizaki Y
Ref : Nature , 409 :685 , 2001
Abstract : The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
ESTHER : Kawai_2001_Nature_409_685
PubMedSearch : Kawai_2001_Nature_409_685
PubMedID: 11217851
Gene_locus related to this paper: mouse-1lipg , mouse-1plip , mouse-1plrp , mouse-ABH15 , mouse-abhd5 , mouse-ABHD6 , mouse-Abhd8 , mouse-aryla , mouse-bphl , mouse-cauxin , mouse-Ces1g , mouse-CPMac , mouse-dpp8 , mouse-EPHX1 , mouse-ES10 , mouse-hslip , mouse-hyes , mouse-ABHD2 , mouse-lcat , mouse-lipli , mouse-LIPN , mouse-lypla1 , mouse-lypla2 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-Ppgb , mouse-PPME1 , mouse-ppt , mouse-q3uuq7 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-RISC , mouse-SERHL , mouse-SPG21 , mouse-Tex30

Title : Identification of a transcriptional activator (ChnR) and a 6-oxohexanoate dehydrogenase (ChnE) in the cyclohexanol catabolic pathway in Acinetobacter sp. Strain NCIMB 9871 and localization of the genes that encode them - Iwaki_1999_Appl.Environ.Microbiol_65_5158
Author(s) : Iwaki H , Hasegawa Y , Teraoka M , Tokuyama T , Bergeron H , Lau PC
Ref : Applied Environmental Microbiology , 65 :5158 , 1999
Abstract : We identified chnR, a gene encoding an AraC-XylS type of transcriptional activator that regulates the expression of chnB, the structural gene for cyclohexanone monooxygenase (CHMO) in Acinetobacter sp. strain NCIMB 9871. The gene sequence of chnE, which encodes an NADP(+)-linked 6-oxohexanoate dehydrogenase, the enzyme catalyzing the fifth step of cyclohexanol degradation, was also determined. The gene arrangement is chnB-chnE-chnR. The predicted molecular masses of the three polypeptides were verified by radiolabeling by using the T7 expression system. Inducible expression of cloned chnB in Escherichia coli depended upon the presence of chnR. A transcriptional chnB::lacZ fusion experiment revealed that cyclohexanone induces chnB expression in E. coli, in which a 22-fold increase in activity was observed.
ESTHER : Iwaki_1999_Appl.Environ.Microbiol_65_5158
PubMedSearch : Iwaki_1999_Appl.Environ.Microbiol_65_5158
PubMedID: 10543838
Gene_locus related to this paper: acisp-CHNC

Title : Complement-induced procoagulant alteration of red blood cell membranes with microvesicle formation in paroxysmal nocturnal haemoglobinuria (PNH): implication for thrombogenesis in PNH - Ninomiya_1999_Br.J.Haematol_106_224
Author(s) : Ninomiya H , Kawashima Y , Hasegawa Y , Nagasawa T
Ref : Br J Haematol , 106 :224 , 1999
Abstract : Complement-induced procoagulant alteration of red blood cell (RBC) membranes in paroxysmal nocturnal haemoglobinuria (PNH) was examined. Microvesicles, deficient in acetylcholinesterase, were generated and released from PNH RBC upon complement activation. The microvesicles generated from complement-activated PNH RBC accelerated factor Xa-dependent plasma coagulation more than those generated from RBC by the treatment with ionophore A23187. When assessed by factor Xa-catalysed prothrombin activation, complement activation enhanced procoagulant properties of both normal and PNH RBC similarly, although PNH RBC were lysed but normal RBC were not. This enhancement of factor Xa-dependent prothrombinase activity of complement-activated RBC was inhibited by the treatment of the RBC with annexin V, a protein with binding affinity for anionic phospholipids especially for phosphatidylserine (PS). Neither the enhanced procoagulant properties of RBC nor apparent RBC population with annexin V-binding affinity were demonstrated before complement activation in any of the four PNH patients studied. PS-externalized PNH RBC and microvesicles may contribute to the removal of PNH RBC from the circulation. We conclude that although PNH RBC do not constantly exhibit enhanced procoagulant properties in vivo, complement activation induces a procoagulant alteration of RBC membranes with microvesicle formation, potentially contributing to the thrombogenesis in PNH.
ESTHER : Ninomiya_1999_Br.J.Haematol_106_224
PubMedSearch : Ninomiya_1999_Br.J.Haematol_106_224
PubMedID: 10444191