PKC? inhibits the hyperglycemia-induced apoptosis signal in adult rat ventricular myocytes

• Published in: Molecular and cellular biochemistry 2005-01, Vol.268 (1-2), p.169-173
• Main Authors: Malhotra, Ashwani, Kang, Barinder P. S., Hashmi, Sayed, Meggs, Leonard G.
• Format: Article
• Language: English
• Subjects: Apoptosis; Kinases; Peptides; Proteins; Rodents; Translocation
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-005-3858-6

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 β^sub I^/β^sub II^, ζ and ε) or activate (PKCε). 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 β^sub I^/β^sub II^ and ζ blocked transmission of the hyperglycemia apoptosis signal, whereas the isozyme specific inhibitor of PKCε (εV1-2) did not alter the magnitude of glucose-induced ARVM apoptosis. Alternatively, the PKCε translocation activator (ψεRACK) abolished hyperglycemia-induced apoptosis, strongly suggesting a cardioprotective role for PKCε in this system. Therefore, we conclude that cardiac PKC isozymes modulate hyperglycemia-induced apoptosis and activation of cardiac PKCε protects ARVM from the hyperglycemia-induced death signal. (Mol Cell Biochem 268: 169-173, 2005)[PUBLICATION ABSTRACT]