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

2018 Fiscal Year Final Research Report

• 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
• Keywords: 活性含硫化合物

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.

Free Research Field

代謝生化学

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。