Regulation of mitochondrial quality control factors and its possibility as a therapeutic target in cardiac failure

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: KOBARA MIYUKI 京都薬科大学, 薬学部, 准教授 (80275198)
• Co-Investigator(Kenkyū-buntansha): MATOBA Satoaki 京都府立医科大学, 医学研究科, 助教 (10305576)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心不全 / ミトコンドリア / 品質管理因子

Outline of Final Research Achievements

Mitochondrial quality control factors, such as fusion factor, OPA1; fission factor, Drp-1; mitophagy-related factor, parkin, have critical roles to mediate mitochondrial morphology and function. The present study examined the regulation of these factors using neonatal cultured myocytes and myocardial infarction (MI) model. Norepinephrine (NE) increased myocytes death and fission mitochondria, though Drp-1 and parkin expressions were not incremented. Hypoxia/reoxygenation (H/R) increased myocytes death, and GLP-1 analogue significantly attenuated. H/R enhanced fragmented and membrane potential- dissipated mitochondria, in association with decreased ATP content. GLP-1 analogue attenuated these morphological and metabolic damages, and attenuated H/R-induced Drp-1 and parkin enhancements.
In vivo MI experiments. Dietary EPA attenuated post-MI remodeling and preserves mitochondrial morphology and function in association with OPA-1 preservation.

Free Research Field

循環器内科学