Functional analyses of sulfur-containing amino acid-derived thiol compounds in the ischemic reperfusion disorder by MALDI MS imaging

• Project/Area Number: 16K01937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Keio University
• Principal Investigator: HISHIKI TAKAKO 慶應義塾大学, 医学部(信濃町), 講師 (10338022)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 活性含硫化合物 / チオール化合物

Outline of Final Research Achievements

The aim of this study is to be clarified the mechanisms that the thiol (containing -SH group) and persulfide (containing -SSH group that is one of the most powerful anti-oxidant thiol compounds) species could reduce intracellular oxidative stresses in the ischemic diseases. First, we performed measurements of the thiol and persulfide in the ischemic mice heart, suggesting that many thiol-containing metabolites play important roles to prevent from heart failure. Besides quantifications of thiol-compounds, we tried the MALDI (Matrix-Assisted Laser/Desorption Ionization) MS imaging for the visualization of the thiol and persulfide on the tissue sections. However, MALDI-MS could oxidize the thiol group easily, making us underestimate the contents of thiol compound on the tissue. Therefore, we apply another method, SERS (Surface-enhanced Raman spectroscopy) imaging technology. SERS enabled us to visualize the tissue distribution of the thiol and persulfide without labelling or staining.

Academic Significance and Societal Importance of the Research Achievements

これまで硫化水素が虚血再灌流障害を軽減する効果を持つことは知られていたが、本研究により硫化水素よりもむしろ、ホモシステイン、システイン、グルタチオン等の含硫アミノ酸にさらに過剰な硫黄原子が結合したパースルフィド化合物が重要であることが示唆された。パースルフィド化合物は様々な生理機能を持つことが近年多数報告されているが、本研究ではこの反応性が高く不安定なパースルフィド化合物を組織切片上で可視化するSERS(Surface-enhanced Raman spectroscopy) imaging技術を確立した。この手法は様々な活性含硫化合物の研究に応用可能な画期的な手法であると確信する。

Research Products

• [Journal Article] Biochemical, metabolomic, and genetic analyses of dephospho coenzyme A kinase involved in coenzyme A biosynthesis in the human enteric parasite Entamoeba histolytica. (2018)
  • Author(s): Nurkanto A, Jeelani G, Yamamoto T, Hishiki T, Naito Y, Suematsu M, Hashimoto T, Nozaki T
  • Journal Title: Frontiers in Microbiology, section Infectious Diseases Volume: 9 Pages: 2902-2902
  • DOI: 10.3389/fmicb.2018.02902
  • NAID: 120007128082
  • Peer Reviewed / Open Access
• [Journal Article] Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure (2018)
  • Author(s): Umbarawan Y, Syamsunarno MRAA, Koitabashi N, Obinata H, Yamaguchi A, Hanaoka H, Hishiki T, Hayakawa N, Sano M, Sunaga H, Matsui H, Tsushima Y, Suematsu M, Kurabayashi M, Iso T
  • Journal Title: Sci Rep Volume: 8(1) Issue: 1 Pages: 12035-12035
  • DOI: 10.1038/s41598-018-30616-1
  • Peer Reviewed / Open Access
• [Journal Article] Development of a Highly Sensitive Device for Counting the Number of Disease-Specific Exosomes in Human Sera. (2018)
  • Author(s): Kabe Y, Suematsu M, Sakamoto S, Hirai M, Koike I, Hishiki T, Matsuda A, Hasegawa Y, Tsujita K, Ono M, Minegishi N, Hozawa A, Murakami Y, Kubo M, Itonaga M, Handa H.
  • Journal Title: Clin Chem Volume: 64 Issue: 10 Pages: 1463-1473
  • DOI: 10.1373/clinchem.2018.291963
  • Peer Reviewed / Open Access
• [Journal Article] Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway (2018)
  • Author(s): Mashima Kyoko、Takahashi Shinichi、Minami Kazushi、Izawa Yoshikane、Abe Takato、Tsukada Naoki、Hishiki Takako、Suematsu Makoto、Kajimura Mayumi、Suzuki Norihiro
  • Journal Title: ASN Neuro Volume: 10 Pages: 1-21
  • DOI: 10.1177/1759091418775562
  • Peer Reviewed / Open Access
• [Journal Article] Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival (2018)
  • Author(s): Shiota M, Naya M, Yamamoto T, Hishiki T, Tani T, Takahashi H, Kubo A, Koike D, Itoh M, Ohmura M, Kabe Y, Sugiura Y, Hiraoka N, Morikawa T, Takubo K, Suina K, Nagashima H, Sampetrean O, Nagano O, Saya H, Yamazoe S, Watanabe H, Suematsu M
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1561-1561
  • DOI: 10.1038/s41467-018-03899-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glucose is preferentially utilized for biomass synthesis in pressure-overloaded hearts: Evidence from fatty acid binding protein-4 and -5 knockout mice. (2018)
  • Author(s): Umbarawan Y, Syamsunarno MRAA, Koitabashi N, Yamaguchi A, Hanaoka H, Hishiki T, Nagahata-Naito Y, Obinata H, Sano M, Sunaga H, Matsui H, Tsushima Y, Suematsu M, Kurabayashi M, Iso T
  • Journal Title: Cardiovasc Res. Volume: - Issue: 8 Pages: 1132-1144
  • DOI: 10.1093/cvr/cvy063
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization and validation of Entamoeba histolytica pantothenate kinase as a novel anti-amebic drug target. (2018)
  • Author(s): Nurkanto A, Jeelani G, Yamamoto T, Naito Y, Hishiki T, Mori M, Suematsu M, Shiomi K, Hashimoto T, Nozaki T
  • Journal Title: Int J Parasitol Drugs Drug Resist. Volume: 8 Issue: 1 Pages: 125-136
  • DOI: 10.1016/j.ijpddr.2018.02.004
  • NAID: 120007134287
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robust suppression of cardiac energy catabolism with marked accumulation of energy substrates during lipopolysaccharide-induced cardiac dysfunction in mice. (2017)
  • Author(s): Umbarawan Y, Syamsunarno MR, Obinata H, Yamaguchi A, Sunaga H, Matsui H, Hishiki T, Matsuura T, Koitabashi N, Obokata M, Hanaoka H, Haque A, Kunimoto F, Tsushima Y, Suematsu M, Kurabayashi M, Iso T
  • Journal Title: Metabolism, clinical and experimental. Volume: - Pages: 47-57
  • DOI: 10.1016/j.metabol.2017.09.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting oxygen sensing prolyl hydroxylase (PHD) for metformin-associated lactic acidosis treatment. (2017)
  • Author(s): Oyaizu-Toramaru T, Suhara T, Hayakawa N, Nakamura T, Kubo A, Minamishima S, Yamaguchi K, Hishiki T, Morisaki H, Suematsu M, Minamishima YA
  • Journal Title: Mol Cell Biol. Volume: 37 (16) Issue: 16
  • DOI: 10.1128/mcb.00248-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure (2017)
  • Author(s): Ono T, Kamimura N, Matsuhashi T, Nagai T, Nishiyama T, Endo J, Hishiki T, Nakanishi T, Shimizu N, Tanaka H, Ohta S, Suematsu M, Ieda M, Sano M, Fukuda K, Kaneda R
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 39752-39752
  • DOI: 10.1038/srep39752
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system. (2016)
  • Author(s): Iizumi T, Takahashi S, Mashima K, Minami K, Izawa Y, Abe T, Hishiki T, Suematsu M, Kajimura M, Suzuki N
  • Journal Title: Neuoinflammation. Volume: １３ Pages: 99-99
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab Volume: 23 Issue: 4 Pages: 663-74
  • DOI: 10.1016/j.cmet.2016.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] マウス水晶体における新規抗酸化物質「過硫化グルタチオン」レベル維持に は，Cystathionine β -synthase (CBS)が必要である (2016)
  • Author(s): 久保 亜紀子，善岡 尊文，後藤 信一，石井 功，菱木 貴子，山本 雄広， 高野 直治，星野 岳郎，中村 貴，吉田 晃敏，梶村 眞弓，末松 誠
  • Organizer: 第41回 日本医用マススペクトル学会
  • Place of Presentation: 愛知県産業労働センター（愛知県名古屋市）
  • Year and Date: 2016-09-15