Molecular adaptation of cellular defences following preconditioning of the heart by repeated ischaemia

作者：Dilip Kumar Das, Richard M. Engelman, Yutaka Kimura · 发表于：Cardiovascular Research · 年份：1993 · DOI：10.1093/cvr/27.4.578 · 被引用次数：217 · 研究领域：Cardiac Ischemia and Reperfusion、Cardiac Fibrosis and Remodeling、Cardiovascular Function and Risk Factors

OBJECTIVE: The molecular mechanism of preconditioning the heart by repeated ischaemia was investigated by examining the expression of stress related and antioxidative genes and proteins. METHODS: Isolated buffer-perfused rat hearts were made ischaemic for 5 min followed by 10 min of reperfusion (1 x PC). Another group of experiments was performed by repeating the ischaemia/reperfusion episode four times (4 x PC). Both 1 x PC and 4 x PC groups were reperfused for 60 min. Control experiments were performed by perfusing the hearts with buffer using the same time frame, but without ischaemia/reperfusion. The induction of the expression of two oncogenes (c-fos and c-myc), three heat shock protein (HSP) genes (HSP 27, HSP 70, and HSP 89 mRNAs) and two antioxidative enzyme genes (Mn-superoxide dismutase (SOD) and catalase mRNAs) by northern hybridisation, as well as the activities of four major antioxidative enzymes (SOD, catalase, glutathione peroxidase, and glutathione reductase) were examined in control and 1 x PC and 4 x PC hearts. In addition, 2-D gel electrophoresis of the proteins in all groups was performed to examine the induction of any new protein. Myocardial preservation was studied by examining left ventricular functions. RESULTS: Northern hybridisation detected enhanced level of c-fos 2.2 kb mRNA and c-myc 2.4 kb mRNA in 4 x PC hearts after 60 min of reperfusion, induction being stronger for c-fos. 1 x PC hearts showed minimal expression of c-fos mRNA, but not c-myc mR...