20-hydroxyeicosatetraenoic Acid Induces Apoptosis Via Activation Of δPKC Signaling Pathways In Neonatal Rat Cardiomyocytes

The ω-hydroxylation product20-hydroxyeicosa-tetraenoic acid (20-HETE)constitutes one of the major arachidonic acid metabolites, which is a potent constrictor ofrenal, cerebral and mesenteric arterioles and small coronary arteries and plays animportant role in the regulation of vascular tone in these vascular beds.In previousstudies, we have found that20-HETE could induce cardiomyocyte apoptosis, but it isunclear which factors mediated this effect. It is clear that PKC involve in apoptosis, thusthe purpose of this study is to explore whether20-HETE induce apoptosis viaPKC-dependent pathways. In this study, we first found that20-HETE could activatePKC by upregulating the mRNA expression of PKC and promoting its translocationfrom the cytoplasm to the mitochondria in primary cultured cardiomyocytes fromneonatal rats. When administration of Rottlerin, PKC inhibitor, was found to inhibit therole of20-HETE-induced apoptosis. This conclusion is supported by the followingobservations:1)20-HETE increased the mRNA expression of PKC in cardiomyocytes;2)20-HETE caused PKC to be translocated from the cytosol to the mitochondria; Asabove provide direct proof that20-HETE activate PKC;3) Rottlerin, PKC inhibitor,inhibited20-HETE-induced cardiomyocyte viability decline and cardiomyocyteapoptosis. These results demonstrate20-HETE activated PKC and participated in theapoptosis trigger the early stage.