δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart

The Cellular response to excessive endoplasmic reticulum (ER) stress includes the activation of signaling pathways, which lead to apoptotic cell death. Here we show that treatment of cultured cardiac myocytes with tunicamycin, an agent that induces ER stress, causes the rapid translocation of delta PKC to the ER. We further demonstrate that inhibition of delta PKC using the delta PKC-specific antagonist peptide, delta V1-1, reduces tunicamycin-induced apoptotic cell death, and inhibits expression of specific ER stress response markers such as CHOP, GRP78 and phosphorylation of JNK. The physiological importance of delta PKC in this event is further supported by our findings that the ER stress response is also induced in hearts subjected to ischernia and reperfusion injury and that this response also involves delta PKC translocation to the ER. We found that the levels of the ER chaperone, GRP78, the spliced XBP-1 and the phosphorylation of JNK are all increased following ischemia and reperfusion and that delta PKC inhibition by delta V1-1 blocks these events. Therefore, ischemia-reperfusion injury induces ER stress in the myocardium in a mechanism that requires delta PKC activitv. Taken together, our data show for the first time that delta PKC activation plays a critical role in the ER stress-mediated response and the resultant cell death. Published by Elsevier Inc.