Development of method for the determination of thiol-containing metabolites using quantitative mass spectrometry

• Project/Area Number: 24651265
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Keio University
• Principal Investigator: HISHIKI TAKAKO 慶應義塾大学, 医学部, 講師 (10338022)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ガスシグナル分子 / チオール化合物 / 硫化水素

Outline of Final Research Achievements

Hydrogen sulfide (H2S), physiological gasseous mediator, plays important roles in regulation of the vascular tone, cytoprotection, and long-term potentiation in hippocampus. In this study, we developed sensitive and quantitative analysis method for H2S and other thiol-containing metabolites, e.g., Cysteine, Cysteine persulfide (Cys-SH), Homocysteine(Hcy), Homocysteine persulfide (Hcy-SH), reduced-glutathione, reduced-glutathione persulfide (GSSH) with mass spectrometric technologies. We tried to quantify the thiol-containing molecules in the hearts of sulfide quinone reductase-like knockdown (SQR-KD) mice using this method. SQR has been identified to be responsible for the initial oxidation of sulfide in mitochondrial matrix. We could detect the higher level of thiol-containing metabolites (H2S, Cysteine persulfide, reduced-glutathione persulfide, and Homocysteine persulfide) in the SQR-KD mice hearts compared with control mice using this useful method.

Research Products

• [Journal Article] Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart. (2015)
  • Author(s): Matsuhashi T, Hishiki T, Zhou H, Ono T, Kaneda R, Iso T, Yamaguchi A, Endo J, Katsumata Y, Atsushi A, Yamamoto T, Shirakawa K, Yan X, Shinmura K, Suematsu M, Fukuda K, Sano M.
  • Journal Title: J Mol Cell Cardiol. Volume: 82 Pages: 116-124
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia. (2015)
  • Author(s): Takenouchi T, Sugiura Y, Morikawa T, Nakanishi T, Nagahata Y, Sugioka T, Honda K, Kubo A, Hishiki T, Matsuura T, Hoshino T, Takahashi T, Suematsu M, Kajimura M.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 1 Pages: 1-12
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry. (2015)
  • Author(s): Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H, Suematsu M.
  • Journal Title: Nitric Oxide. Volume: 30 (46) Pages: 102-13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Large-area surface-enhanced Raman spectroscopy imaging of brain ischemia by gold nanoparticles grown on random nanoarrays oftransparent boehmite, (2015)
  • Author(s): 1.Yamazoe S, Naya M, Shiota M, Morikawa M, Kubo A, Tani T, Hishiki T, Horiuchi T, Suematsu M, and Kajimura M
  • Journal Title: ACS Nano Volume: 8 Issue: 6 Pages: 5622-5632
  • DOI: 10.1021/nn4065692
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neutral aminoaciduria in cystathionine β-synthase-deficient mice; an animal model of homocystinuria. (2014)
  • Author(s): Akahoshi N, Kamata S, Kubota M, Hishiki T, Nagahata Y, Matsuura T, Yamazaki C, Yoshida Y, Yamada H, Ishizaki Y, Suematsu M, Kasahara T, Ishii I.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 306(12) Issue: 12 Pages: F1462-F1476
  • DOI: 10.1152/ajprenal.00623.2013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway. (2014)
  • Author(s): Takehiro Yamamoto, Naoharu Takano, Kyoko Ishiwata, Mitsuyo Ohmura, Yoshiko Nagahata, Tomomi Matsuura, Aki Kamata, Kyoko Sakamoto, Tsuyoshi Nakanishi, Akiko Kubo, Takako Hishiki, and Makoto Suematsu.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3480-3480
  • DOI: 10.1038/ncomms4480
  • Peer Reviewed
• [Journal Article] A critical role of fatty acid binding protein 4 and 5 (FABP4/5) in the systemic response to fasting (2013)
  • Author(s): Syamsunarno MR, Iso T, Hanaoka H, Yamaguchi A, Obokata M, Koitabashi N, Goto K, Hishiki T, Nagahata Y, Matsui H, Sano M, Kobayashi M, Kikuchi O, Sasaki T, Maeda K, Murakami M, Kitamura T, Suematsu M, Tsushima Y, Endo K, Hotamisligil GS, Kurabayashi M
  • Journal Title: PLoS One Volume: 14;8 Issue: 11 Pages: e79386-e79386
  • DOI: 10.1371/journal.pone.0079386
  • Peer Reviewed
• [Journal Article] Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in fatty acid uptake in heart and skeletal muscle (2013)
  • Author(s): Iso Tatsuya, Kurabayashi Masahiko
  • Journal Title: Arteriosclerosi Thrombosis and Vascular Biology Volume: vol.33 Issue: 11 Pages: 2549-2557
  • DOI: 10.1161/atvbaha.113.301588
  • Peer Reviewed
• [Journal Article] Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo. (2013)
  • Author(s): Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA.
  • Journal Title: Mol Cancer Res. Volume: 11 Issue: 9 Pages: 973-985
  • DOI: 10.1158/1541-7786.mcr-12-0669-t
  • Peer Reviewed
• [Journal Article] Distinct Metabolic Flow Enable Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes. (2013)
  • Author(s): Tohyama S, Hattori F, Sano M, et al.
  • Journal Title: Cell Stem Cell Volume: 12 Issue: 1 Pages: 127-37
  • DOI: 10.1016/j.stem.2012.09.013
  • Peer Reviewed
• [Journal Article] ガス分子を量る：チオールプローブを用いたH2Sの定量 (2013)
  • Author(s): 菱木貴子
  • Journal Title: 実験医学 別冊 Volume: 36 Pages: 132-143
• [Journal Article] Mitochondrial dysfunction associated with increased oxidative stress and -synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue. (2012)
  • Author(s): Imaizumi Y
  • Journal Title: Mol Brain Volume: 5 Issue: 1 Pages: 35-35
  • DOI: 10.1186/1756-6606-5-35
  • Peer Reviewed
• [Journal Article] Gas biology : Tiny molecules controlling metabolic systems (2012)
  • Author(s): Kajimura M., Nakanishi T., Takenouchi T., Morikawa T., Hishiki T., Yukutake Y., and Suematsu M.
  • Journal Title: Respiratory Physiology & Neurobiology Volume: (in press) Issue: 2 Pages: 139-148
  • DOI: 10.1016/j.resp.2012.03.016
  • Peer Reviewed
• [Journal Article] Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine gamma-lyase, an animal model of cystathioninuria. (2012)
  • Author(s): Yamada H, Akahoshi N, Kamata S, Hagiya Y, Hishiki T, Nagahata Y, Matsuura T, Takano N, Mori M, Ishizaki Y, Izumi T, Kumagai Y, Kasahara T, Suematsu M, Ishii I
  • Journal Title: Free Radic Biol Med Volume: 52 Issue: 9 Pages: 1716-1726
  • DOI: 10.1016/j.freeradbiomed.2012.02.033
  • Peer Reviewed
• [Journal Article] がん代謝システムの顕微質量イメージングによる解析 (2012)
  • Author(s): 末松誠、久保亜紀子、大村光代、菱木貴子、梶村眞弓、加部泰明、杉浦悠毅
  • Journal Title: 実験医学 増刊 Volume: 30 Pages: 193-202
• [Presentation] 解糖系酵素PFKFB3のメチル化制御はがん細胞の酸化ストレス耐性獲得に重要である (2013)
  • Author(s): 山本雄広、石渡恭子、高野直治、大村光代、菱木貴子、長畑善子、末松誠
  • Organizer: 第86回 日本生化学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] アルギニンメチル化酵素PRMT1の細胞内局在を反映した糖代謝酵素の核内メチル化機構 (2013)
  • Author(s): 山本雄広、石渡恭子、高野直治、大村光代、菱木貴子、長畑善子、末松誠
  • Organizer: 第36回 日本分子生物学会本大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] Sensitive detection and quantification of hydrogen sulfide as a gasotransmitter by combining monobromobimane-based derivatization to triple quadrupole LC/MS/MS (2012)
  • Author(s): Takako Hishiki , Tsuyoshi Nakanishi and Makoto Suematsu
  • Organizer: American Society for Mass Spectrometry
  • Place of Presentation: Vancouver, BC, Canada