Study of Ethyl-2-methylquinoline-3-carboxylate in Ischaemia and Reperfusion Induced Myocardial Injury as specific inhibitor of GCN-5.

Abstract

Myocardial Infarction is the leading cause of death and disability worldwide. It has been reported that GCN-5 inhibitors inhibit GCN-5 mediated acetylation of PGC-1 alpha, which in turns enhances PGC-1alpha activity, mitochondrial function and oxidative metabolism. PGC-1α activity is regulated by Histone deacetylases and Histone acetyl transferases. In particularly PGC-1α is directly acetylated by HAT enzyme-general control non derepressible 5 (GCN-5). Ethyl-2-methylquinoline-3-carboxylate is reported to be a specific inhibitor of GCN-5. PGC-1 α levels are reported to be reduced in heart following myocardial infarction and up regulation of PGC-1 α confers protection against ischaemia and reperfusion in cardiomyoblast cells. Thus, in present study we investigated the protective effect of Ethyl-2-methyl quinoline-3-carboxylate as GCN-5 inhibitor in modulation of PGC-1 alpha activity during ischemia and reperfusion induced myocardial injury.