Search

Abstract Recruitment of the protein kinase C (PKC) family of isozymes is an integral component of the signaling events that direct cardiac phenotype expressed during postnatal development and in response to pathologic stimuli. Hyperglycemia is a potent activating signal for cardiac PKC isozymes and induces the apoptosis program in cardiac muscle cells. To determine whether cardiac PKC isozymes modulate transmission of the hyperglycemia apoptosis signal, we have employed isozyme-specific peptide modulators to selectively inhibit (PKC I / II , ? and e) or activate (PKCe). PKC peptides were delivered to primary cultures of serum starved adult rat ventricular myocytes (ARVM), by conjugation to the homeodomain of drosophila antennapedia. As expected, hyperglycemia induced a 35% increase in ARVM apoptosis. Peptide inhibitors of PKC I / II and ? blocked transmission of the hyperglycemia apoptosis signal, whereas the isozyme specific inhibitor of PKCe (eV1-2) did not alter the magnitude of glucose-induced ARVM apoptosis. Alternatively, the PKCe translocation activator (?eRACK) abolished hyperglycemia-induced apoptosis, strongly suggesting a cardioprotective role for PKCe in this system. Therefore, we conclude that cardiac PKC isozymes modulate hyperglycemia-induced apoptosis and activation of cardiac PKCe protects ARVM from the hyperglycemia-induced death signal. (Mol Cell Biochem 268 : 169173, 2005) [ABSTRACT FROM AUTHOR]