Biomedical Application of Gas Biology through Multidisciplinary Approaches

2009 Fiscal Year Final Research Report

• Project/Area Number: 17GS0419
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Keio University
• Principal Investigator: SUEMATSU Makoto Keio University, 医学部, 教授 (00206385)
• Co-Investigator(Kenkyū-buntansha): SAITOU Masao 東北大学, 多元物質研究所, 教授 (70302239) ; SOGA Tomoyoshi 慶應義塾大学, 環境情報学部, 教授 (60338217) ; HIRAO Atsushi 金沢大学, がん研究所, 教授 (90343350) ; TANAKA Hirotoshi 東京大学, 医科学研究所, 准教授 (00171794)
• Project Period (FY): 2005 – 2009
• Keywords: 一酸化炭素 / ガスバイオロジー / 酸素センサー / メタボローム / cytochrome oxidase / 構造生物学 / ミトコンドリア / Hypoxia inducible factor

Research Abstract

The multiplicity of gas actions and gas targets and the difficulty in measuring local gas concentrations obscures detailed mechanisms whereby gases exert their actions, and many questions remain unanswered. In this project, advanced mass spectrometry combined with high-performance computer technology allowed us to mine biological mechanisms for gas-responsive signal transducing systems. We also take an integrated approach to the interaction of gases by considering the physiological significance of CO, NO, and H2S on metabolic systems and energy-supporting enzyme systems including cytochrome c oxidase, a key target and central mediator of mitochondrial respiration. By evaluating gas-mediated control functions from both in vitro and in vivo perspectives, we attempted to elaborate on the complex multiple interactions of O(2), NO, CO, and H2S

Research Products

• [Journal Article] Regulation of the HIF-1α level is essential for hematopoietic stem cells. (2010)
  • Author(s): Takubo K, Goda N, Yamada W, Ikeda E Kubota Y, Shima H Johnson RS, Hirao A, Suematsu M, Suda T
  • Journal Title: Cell Stem Cell (in press)
• [Journal Article] Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry. (2010)
  • Author(s): Hattori K, Kajimura M, Nakanishi T, Fujiwake H, Ogawa K, Nagahata Y, Hishiki T, Kubo A, Setou M, Suematsu M
  • Journal Title: Antioxid Redox Signal (In press)
• [Journal Article] von Hippel-Lindau protein regulates transition from fetal to adult circulatory system in retina. (2010)
  • Author(s): Kurihara T, Kubota Y, Ozawa Y, Takubo K, Noda K, M. Simon C, Johnson RS, Suematsu M, Tsubota K, Ishida S, Goda N, Suda T, Okano H
  • Journal Title: Development 137(9) Pages: 1563-1571
• [Journal Article] Interactions of multiple gas-transducing systems: Hallmarks and uncertainties of CO, NO and H2S gas biology. (2010)
  • Author(s): Kajimura M, Fukuda R, Bateman RM, Yamamoto T, Suematsu M
  • Journal Title: Antioxid Redox Signal (In press)
• [Journal Article] TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. (2010)
  • Author(s): Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, Nakao S, Motoyama N, Hirao A
  • Journal Title: Nature 463 Pages: 676-680
• [Journal Article] Metabolic remodeling induced by mitochondrial aldehyde stress stimulates tolerance to oxidative stress in the heart. (2009)
  • Author(s): Endo J, Sano M, Katayama T, Hishiki T, Shinmura K, Morizane S, Matsuhashi T, Katsumata Y, Zhang Y, Ito H, Nagahata Y, Marchitti S, Nishimaki K, Wolf AM, Nakanishi H, Hattori F, Vasiliou V, Adachi T, Ohsawa I, Taguchi R, Hirabayashi Y, Ohta S, Suematsu M, Endo J, Sano M, K
  • Journal Title: Circ Res 105(11) Pages: 1118-1127
• [Journal Article] Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin. (2009)
  • Author(s): Tamase A, Muraguchi T, Naka K, Tanaka S, Kinoshita M, Hoshii T, Ohmura M, Shugo H, Ooshio T, Nakada M, Sawamoto K, Onodera M, Matsumoto K, Oshima M, Asano M, Saya H, Okano H, Suda T, Hamada JI, Hirao A
  • Journal Title: Proc Natl Acad Sci U S A. 106 Pages: 17163-17168
• [Journal Article] Measurement of Internal Body Time by Blood Metabolomics. (2009)
  • Author(s): Minami, Y., Kasukawa, T., Kakazu, Y., Iigo, M., Sugimoto, M., Ikeda, S., Yasui, A., van der Horst, G., Soga, T., Ueda, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 9890-9895
• [Journal Article] Ligand-based gene expression profiling identifies critical role of glucocorticoid receptor in rat neonatal cardiomyocytes. (2009)
  • Author(s): Yoshikawa N, Nagasaki M, Sano M, Tokudome S, Ueno K, Shimizu N, Imoto S, Miyano S, Suematsu M, Fukuda K, Morimoto C, Tanaka H
  • Journal Title: Am J Physiol Endocrinol Metab 296(6) Pages: E1363-1373
• [Journal Article] Quantitative Metabolome Profiling of Colon and Stomach Cancer Microenvironment by Capillary Electrophoresis Time-of-flight Mass Spectrometry. (2009)
  • Author(s): Hirayama, A., Kami, K., Sugimoto, M., Sugawara, M., Toki, N., Onozuka, H., Kinoshita, T., Saito, N., Ochiai, A., Tomita, M., Esumi, H., *Soga, T.
  • Journal Title: Cancer Res 69 Pages: 4918-4925
• [Journal Article] Metabolomic Profiling of Anionic Metabolites by Capillary Electrophoresis Mass Spectrometry. (2009)
  • Author(s): Soga, T., Igarashi, K., Itoh, C., Mizobuchi, K., Zimmermann, H., Tomita, M.
  • Journal Title: Anal. Chem 81 Pages: 6165-6174
• [Journal Article] Metabolite profiling reveals YihU as a novel hydroxybutyrate dehydrogenase for alternative succinic semialdehyde metabolism in Escherichia coli. (2009)
  • Author(s): Saito, N., Robert, M., Kochi, H., Matsuo, G., Kakazu, Y., Soga, T., Tomita, M.
  • Journal Title: J. Biol. Chem. 109 Pages: 16442-16451
• [Journal Article] Rescue of anemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes. (2009)
  • Author(s): Iuchi, Y., Okada, F., Takamiya, R., Kibe, N., Tsunoda, S., Nakajima, O., Toyoda, K., Nagae, R., Suematsu, M., Soga, T., Uchida, K., Fujii, J.
  • Journal Title: Biochem. J 422 Pages: 313-320
• [Journal Article] HIF-1α is necessary to support gluconeogenesis during liver regeneration Biochem. Biophys. (2009)
  • Author(s): Tajima, T., Goda, N., Fujiki, N., Hishiki, T., Nishiyama, Y., Senoo-Matsuda, N., Shimazu, M., Soga, T., Yoshimura, Y., Johnson, R.S., Suematsu, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 387 Pages: 789-794
• [Journal Article] Mono-(2-ethylhexyl) phthalate Targets Glycogen Debranching Enzyme and Affects Glycogen Metabolism in Rat Testis. (2009)
  • Author(s): Kuramori, C., Hase, Y., Hoshikawa, K., Watanabe, K., Nishi, T., Hishiki, T., Soga, T., Nashimoto, A., Kabe, Y., Yamaguchi, Y., Watanabe, H., Kataoka, K., Suematsu, M., Handa, H.
  • Journal Title: Toxicol. Sci 109 Pages: 143-151
• [Journal Article] Cystathionine β-synthase as a Carbon Monoxide-sensitive Regulator of Bile Excretion. (2009)
  • Author(s): Shintani, T., Iwabuchi, T., Soga, T., Kato, Y., Yamamoto, T., Takano, N., Hishiki, T., Ueno, Y., Ikeda, S., Sakurakawa, T., Ishikawa, K., Goda, N., Yitagawa, Y., Kajiyama, M., Matsumoto, K., Suematsu, M.
  • Journal Title: Hepatology 49 Pages: 141-150
• [Journal Article] Identification of Stem Cells During Prepubertal Spermatogenesis Via Monitoring of Nucleostemin Promoter Activity. (2008)
  • Author(s): Ohmura M, Naka K, Hoshii T, Muraguchi T, Shugo H, Tamase A, Uema N, Ooshio T, Arai F, Takubo K, Nagamatsu G, Hamaguchi I, Takagi M, Ishihara M, Sakurada K, Miyaji H, Suda T, *Hirao A
  • Journal Title: Stem Cells 26 Pages: 3237-3246
• [Journal Article] Exacerbating Role of γδ T Cells in Chronic Colitis of T Cell Receptor αMutant Mice. (2008)
  • Author(s): Nanno, M., Kanari, Y., Naito, T., Inoue, N., Hisamatsu, T., Chinen, H., Sugimoto, K., Shimomura, Y., Yamagishi, H., Shiohara, T., Ueha, S., Matsushima, K., Suematsu, M., Mizoguchi, A., Hibi, T., Bhan, A.K., Ishikawa, H
  • Journal Title: Gastroenterology 134 Pages: 481-490
• [Journal Article] Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia. (2008)
  • Author(s): Akahoshi N, Kobayashi C, Ishizaki Y, Izumi T, Himi T, Suematsu M, Ishii I
  • Journal Title: Hum. Mol. Genet 17 Pages: 1994-2005
• [Journal Article] Multiple Highthroughput Analyses Monitor The Response of E. coli to Perturbations" (2007)
  • Author(s): Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P.Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., AraIshii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba
  • Journal Title: Science 316 Pages: 593-597
• [Journal Article] A peptide bond provides unidirectional respiratory proton pumping in bovine cytochrome c oxidase. (2007)
  • Author(s): Shimokata K, Katayama Y, Murayama H, Suematsu M, Tsukihara T, Muramoto K, Yoshikawa S, Shimada H
  • Journal Title: Proc Natl Acad Sci USA 104(10) Pages: 4200-4205
• [Journal Article] Method for determination of association and dissociation rate constants of reversible biomolecular reactions by isothermal titration calorimeters. (2007)
  • Author(s): Egawa, T., Tsuneshige, A., Suematsu, M., Yonetani, T
  • Journal Title: Anal. Biochem 79(7) Pages: 2972-2978
• [Journal Article] Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution. (2007)
  • Author(s): Hangai-Hoger, N., Tsai, A.G., Carbales, P., Suematsu, M., Intaglietta, M
  • Journal Title: Crit Care Med 35(4) Pages: 1123-1132
• [Journal Article] Roles of hemoglobin allostery in hypoxia-induced metabolic alterations in erythrocytes: simulation and its verification by metabolome analysis. (2007)
  • Author(s): Kinoshita, A., Tsukada, K., Soga, T., Hishiki, T., Ueno, Y., Nakayama, Y., Tomita, M., Suematsu, M.
  • Journal Title: J Biol Chem 282(14) Pages: 10731-10741
• [Journal Article] Menage-a-Trois 1 is critical for the transcriptional function of PPARgamma coactivator 1. (2007)
  • Author(s): Sano M, Izumi Y, Helenius K, Asakura M, Rossi DJ, Xie M, Taffet G, Hu L, Pautler RG, Wilson CR, Boudina S, Abel ED, Taegtmeyer H, Scaglia F, Graham BH, Kralli A, Shimizu N, Tanaka H, Makela TP, Schneider MD
  • Journal Title: Cell Metab 5(2) Pages: 129-142
• [Journal Article] Visualization of three-way comparisons of omics data. (2007)
  • Author(s): Baran, R., Robert, M., Suematsu, M., Soga, T., Tomita, M.
  • Journal Title: BMC Bioinformatics 8(1) Pages: 72e
• [Journal Article] Curriculum vitae of intestinal intraepithelial T cells: their developmental and behavioral characteristics. (2007)
  • Author(s): Ishikawa H, Naito T, Iwanaga T, Takahashi-Iwanaga H, Suematsu M, Hibi T, Nanno M
  • Journal Title: Immunol Rev 215 Pages: 154-165
• [Journal Article] Regulation of reactive oxygen species by atm is essential for proper response to DNA double-strand breaks in lymphocytes. (2007)
  • Author(s): Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M, Naka K, Azuma M, Miyamoto K, Hosokawa K, Ikeda Y, Mak TW, Suda T, Hirao A
  • Journal Title: J Immunol 178 Pages: 103-110
• [Journal Article] MathDAMP: a package for differential analysis of metabolite profiles. (2006)
  • Author(s): Baran, R., Kochi, H., Saito, N., Suematsu, M., Soga, T., Nishioka, T., Robert, M., Tomita, M.
  • Journal Title: BMC Bioinformatics 7 Pages: 530e
• [Journal Article] Design of metal cofactors activated by a protein-protein electron transfer system. (2006)
  • Author(s): Ueno T, Yokoi N, Unno M, Matsui T, Tokita M, Yamada M, Ikeda-Saito M, Nakajima H, Watanabe Y
  • Journal Title: Proc Natl Acad Sci USA 103, 14 Pages: 9416-9421
• [Journal Article] Compound I of heme oxygenase cannot hydroxylate its heme meso-carbon J. Am. (2006)
  • Author(s): Matsui T, Kim SH, Jin H, Hoffman BM, Ikeda-Saito M
  • Journal Title: J. Am. Chem. Soc 128 Pages: 1090-1091
• [Journal Article] T-state stabilization of hemoglobin allostery by nitric oxide: a protection against post-ischemic hepatobiliary dysfunction. (2006)
  • Author(s): Suganuma K, Tsukada K, Tsuneshige A, Kashiba M, Yonetani T, Suematsu M
  • Journal Title: Antioxid Redox Signal 8 Pages: 1847-1855
• [Journal Article] Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. (2006)
  • Author(s): Soga T, Baran R, Suematsu M, Ueno Y, Ikeda S, Sakuragawa T, Kakazu Y, Ishikawa T, Robert M, Nishioka, T., Tomita, M.
  • Journal Title: J Biol Chem 281(24) Pages: 16768-16776
• [Journal Article] Maintaining the redox balance intact: gosha-jinki-gan but not insulin activates guanylate cyclase in diabetic rats. (2006)
  • Author(s): Cameron-Scaefer S, Kondo K, Ishige A, Tsuyama S, Uchida K, Hanawa T, Suematsu M, Watanabe K.
  • Journal Title: Ophthalmic Res 38(2) Pages: 95-104
• [Journal Article] Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury. (2006)
  • Author(s): Miyao N, Suzuki Y, Takeshita K, Kudo H, Ishii M, Hiraoka R, Nishio K, Tamatani T, Sakamoto S, Suematsu M, Tsumura H, Ishizaka A, Yamaguchi K
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 290 Pages: L1059-L1068
• [Journal Article] O2-and H2O2-dependent verdoheme degradation by heme oxygenase: Reaction mechanisms and potential physiological roles of the dual pathway degradation J (2005)
  • Author(s): Matsui T, Nakajima A, Fujii H, Mansfield K, Matera C. Migita T, Yoshida T, Ikeda-Saito M.
  • Journal Title: Biol Chem 280 Pages: 36833-40
• [Journal Article] Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: Identification of??-ketoglutarate decarboxylase. (2005)
  • Author(s): Tian J, Bryk R, Itoh M, Suematsu, M, Nathan C
  • Journal Title: Proc Natl Acad Sci USA 102 Pages: 10670-10675
• [Journal Article] Carbon monoxide from heme oxygenase-2 is a tonic regulator against nitric oxide-dependent vasodilatation in the adult rat cerebral microcirculation. (2005)
  • Author(s): Ishikawa M, Kajimura M, Adachi T, Maruyama K, Makino N, Goda N, Yamaguchi T, Sekizuka E, Suematsu M
  • Journal Title: Circ Res 97(12) Pages: e104-e114
• [Journal Article] Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver. (2005)
  • Author(s): Fujii K, Sakuragawa T, Kashiba M, Sugiura Y, Maruyama K, Goda N, Nimura Y, Suematsu M
  • Journal Title: Antioxid Redox Signal 7(5-6) Pages: 788-794
• [Journal Article] Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes. (2005)
  • Author(s): Sugiura, Y., Kashiba, M., Hoshikawa, K., Sasaki, R., Saito, K., Kimura, H., Maruyama, K., Goda, N., Suematsu M.
  • Journal Title: Antioxid. Redox Signal 7(5-6) Pages: 781-787
• [Presentation] Biomedical application of metabolome analysis to mine gaseous signal transducers in the liver (2007)
  • Author(s): Suematsu M
  • Organizer: APS Symposium: Frontiers in the Cellular and Molecular Physiology of the Hepatic Microcirculation. for EB2007
  • Place of Presentation: Invited Lecture. Washington DC
  • Year and Date: 2007-04-29
• [Presentation] Metabolome analyses reveal roles of cystathionine beta synthase as a CO-responsive metabolic regulator in mammals (2006)
  • Author(s): Suematsu M
  • Organizer: In NO and CO: distinct biological properties. The 20th IUBMB Symposium
  • Place of Presentation: Organizer, Kyoto
  • Year and Date: 20060619-20060622
• [Presentation] Biomedical application of metabolome analysis (2006)
  • Author(s): Suematsu M
  • Organizer: Harvard-Kitasato Symposium for Critical Path for Translational Research
  • Place of Presentation: Tokyo(Invited Lecture)
  • Year and Date: 2006-10-24
• [Presentation] Erythrocytes as an oxygen-sensing metabomic sink determining microvascular tone (2005)
  • Organizer: IUPS Plenary Symposium
  • Place of Presentation: San Diego CA
  • Year and Date: 20050405-20050408
• [Presentation] Carbon monoxide as a guardian against the liver injury (2005)
  • Author(s): Suematsu M
  • Organizer: Plenary Lecture
  • Place of Presentation: ISBRA Satellite Symposium
  • Year and Date: 2005-09-02