Comprehennsive analysis of cerebral metabolic changes during ischemia-reperfusion by omics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10302
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kobe University
• Principal Investigator: Hosoda Kohkichi 神戸大学, 医学研究科, 医学研究員 (90403261)
• Co-Investigator(Kenkyū-buntansha): 篠山 隆司 神戸大学, 医学部附属病院, 講師 (10379399) ; 甲村 英二 神戸大学, 医学研究科, 教授 (30225388) ; 篠原 正和 神戸大学, 医学(系)研究科(研究院), 研究員 (80437483)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 脳虚血 / メタボロミクス / ペントースリン酸 / NADPH

Outline of Final Research Achievements

We performed comparative metabolic analysis of reperfusion effect on cerebral metabolism using rat middle cerebral artery occlusion (MCAO). Gas-chromatography/mass-spectrometry analysis showed metabolic changes that depended on reperfusion time. Enrichment analysis showed pentose phosphate pathway (PPP) was significantly upregulated during ischemia-reperfusion. Immunoblotting showed gradual increase in HSP27 and marked increase in HSP27 phosphorylation. G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. ATM kinase inhibitor significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size after reperfusion. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant system during ischemia-reperfusion.

Free Research Field

脳神経外科学