Involvement of p53 in the Responses of Cardiac Muscle Cells to Heat Shock Exposure and Heat Acclimation

Intense heat stress induces damage to the heart, whereas mild to moderate heat stress protects the heart against subsequent ischemic injury. The mechanisms underlying the detrimental and beneficial effects of heat stress remain unclear. In this study, we investigated the role of p53 in the responses of cardiac muscle cells to acute heat exposure and heat acclimation (HA). Heat exposure increased the levels of caspase and annexin, and levels of cytosolic, nuclear, and mitochondrial p53 protein in H9c2 cells. Pifithrin-α or pifithrin-μ reduced heat-induced apoptotic response in these cells. HA reduced localization of p53 in the mitochondria and improved cell viability during heat exposure. The effects of heat exposure and HA on p53 were further verified in vivo in mouse heart tissue. These results suggest that p53 plays a role in heat-induced apoptosis in cardiac muscle cells. The protective effect of HA against heat injury likely involves a p53-dependent mechanism.