2005 Fiscal Year Final Research Report Summary

Studies on the molecular and protective mechanisms of carbon monoxide on the ischemia, intoxication and infection.

Research Project

Project/Area Number	16590534
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Legal medicine
Research Institution	The University of Tokyo
Principal Investigator	UEMURA Koichi The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (30244586)
Co-Investigator(Kenkyū-buntansha)	YOSHIDA Ken-ichi The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40166947)
Project Period (FY)	2004 – 2005
Keywords	carbon monoxide / ischemia / reactive oxygen species / necrosis / apoptosis / calcium / H9c2 / L-type Ca^<2+> channel
Research Abstract	Carbon monoxide (CO) is known to protect myocardial and vascular cells against injuries due to ischemia-reperfusion or inflammation. We showed that a C^<2+>-dependent protease calpain promotes necrotic cell death of cardiomyocyte-derived H9c2 cells due to hypoxia through α-fodrin proteolysis. Here, we show that ischemia induces necrotic cell death, which is inhibited by either CO, extracellular Ca^<2+> deprivation or L-type Ca^<2+> channel blockers. A whole cell patch clamp experiments supports that CO inhibits L-type Ca^<2+> channel mediated influx of Ca^<2+> and the ischemic death of H9c2 cells.