SIMULTANEOUS OVEREXPRESSION OF 2 STRESS PROTEINS IN RAT CARDIOMYOCYTES AND MYOGENIC CELLS CONFERS PROTECTION AGAINST ISCHEMIA-INDUCED INJURY

Background Mitochondria are known to be a major target during ischemic cardiac injury. Previous studies have shown that in rodent myogenic c ells and in the hearts of transgenic mice in which the heat shock or s tress protein 70 is increased, there is a marked tolerance to ischemia /reperfusion injury. Two other heat shock proteins (HSP60 and HSP10) a re known to form, within the mitochondria, a chaperonin complex that i s important for mitochondrial protein folding and function. We were th en interested in investigating whether increased expression of these t wo stress proteins is able to protect myogenic cells against ischemia/ reperfusion injury. Methods and Results We generated recombinant adeno viral vectors containing HSP60, HSP10, or a combination of the two gen es. These adenoviral constructs overexpress significant amounts of the se stress proteins in both rat neonatal cardiomyocytes and the myogeni c H9 c2 cell line. Cells infected with an adenoviral construct overexp ressing both HSP60 and HSP10 were found to be protected against simula ted ischemia, whereas cells infected with adenoviral constructs overex pressing only HSP60 or HSP10 alone were not rendered tolerant to simul ated ischemic injury. Conclusions These results suggest that the simul taneous expression of these two proteins that form a chaperonin comple x in the mitochondria plays an important role in the survival of myoge nic cells after ischemia/reperfusion injury.