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Influence of PKC- overexpression on HSP70 and cardioprotection

Department of Physiology and Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois

Submitted 2 October 2006 ; accepted in final form 16 December 2006

Recent research has indicated that the protein kinase C (PKC) isoforms and the heat shock proteins (HSPs) are involved in cardioprotection. We have investigated the possible interaction between these two protein families. We have found that adenoviral-mediated expression of PKC- in neonatal rat ventricular myocytes (NRVM) not only increases the expression of HSP70 but also protects against simulated ischemia-reperfusion. In addition, Western blots of PKC--infected NRVM indicated that other HSPs are not induced in the same manner as HSP70. In an effort to determine the mechanism of induction of HSP70 by PKC-, we tested a chimeric construct that linked the luciferase reporter gene to the 5'-promoter region of HSP70 in myogenic H9c2 cells. When PKC- was expressed, the 5'-promoter region of the HSP70 responded robustly, indicating that PKC- induction of HSP70 expression is through transcription activation. Electrophoretic mobility shift assay determined that overexpression of PKC-, PKC-, or PKC- did not induce activation of heat shock factor-1 (HSF-1). Therefore, induction of HSP70 by PKC- is independent of heat shock factor-1 activation. We also measured cellular injury by assessing creatine kinase (CK) release from NRVM after simulated ischemia to determine cardioprotection. NRVM infected with the wild-type adenoviral construct AdwtPKC- released 54% less CK than control NRVM. Experiments using small interfering RNA against HSP70 indicate that loss of PKC--induced HSP70 expression results in increased CK release or a loss of protection. Our results show that there is a close interaction between PKC- and HSP70, independent of heat shock factor-1 activation, and that the protection conferred by PKC- overexpression is mediated by the transcriptionally induced expression of HSP70.

heat shock proteins; neonatal rat ventricular myocytes; ischemia-reoxygenation; simulated ischemia