HSP27 PLAYS A DOMINANT ROLE IN INTERFERING WITH THE EXTRINSIC-APOPTOTIC PATHWAY

Abstract

The molecular chaperone, heat shock protein 27 (Hsp27) regulates cell apoptosis by interacting directly with the caspase activation components in the apoptotic pathways. With the assistance of the Tat protein transduction domain we directly delivered the Hsp27 into H9c2 cells and demonstrate that this protein can reverse hypoxia-induced apoptosis of cells. Cellular apoptosis can be induced by mitochondria-dependent (intrinsic) and-independent (extrinsic) pathways. In order to characterize the contribution of Hsp27 in blocking the two major apoptotic pathways operational within cells, we exposed H9c2 cells to staurosporine and cobalt chloride, agents that induce intrinsic and extrinsic pathways of apoptosis in cells respectively. The Tat-Hsp27 fusion protein showed a greater propensity to inhibit the effect induced by the cobalt chloride treatment by interfering with the components of the extrinsic pathway of apoptosis. These results will be useful in prevention of human disease conditions that prevail due to the activation of extrinsic apoptotic pathways.