Hsp70 may protect cardiomyocytes from stress-induced injury by inhibiting Fas-mediated apoptosis

Abstract

Expression of Hsp70 is an endogenous mechanism by which living cells adapt to stress and the protection of Hsp70 may interfere with the apoptotic machinery in a variety of ways. Here, we observed the change of Hsp70 expression in rat myocardium under stress and explored the protective effect of Hsp70 on the Fas-mediated pathway to cardiomyocyte apoptosis. The results showed that restraint stress led to cardiac dysfunction and structural damage of the myocardium, as well as activation of the Fas pathway. A similar increase in the Fas expression level, caspase-8/3 activity, and the apoptotic rate of the cardiomyocyte also were found, which indicated that Fas-mediated apoptosis of cardiomyocytes might be one of the mechanisms of cardiomyocyte injury induced by stress. Changes in Hsp70 levels and distribution occurred during the stress process, which correlated with the severity of myocardium injury. Heat preconditioning induced the upregulation of Hsp70 synthesis, which in turn may have mitigated subsequent restraint stress-induced damage, including electrocardiography (ECG) abnormality, myocardium damage, and cell death. Moreover, Hsp70 overexpression induced by heat preconditioning had no effect on Fas expression in the cardiomyocyte, but could inhibit activation of caspase-8/3 induced by the Fas signaling pathway and, as a result, prevent cell apoptosis. These results suggest that Hsp70 is capable of protecting the cardiomyocyte from stressinduced injury by inhibiting Fas-mediated apoptosis, and Hsp70 could be considered a target in future drugs to prevent cardiovascular injury caused by stress.

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

“…However, the molecular mechanism of this anti-apoptotic effect mediated by Hsps is still unclear and it is possible that, under certain circumstances, may be due by a variety of different modulators [34]. It has been shown that Hsp70 can inhibit apoptosis by interacting with a member of the Fas death-inducing signaling upstream of Caspase-8 [37,38]. Hsp70, during oxidative stress, can stabilize Bcl-2, protecting the cell against apoptosis [39].…”

Interaction of serum 70-kDa heat shock protein levels and HspA1B (+1267) gene polymorphism with disease severity in patients with chronic heart failure

“…It is conceivable that Hsp70 can represent a protective mechanism as well. In animal models, overexpression of Hsp70 protects the heart against damaging effects of ischaemia (Trost et al 1998) or against stress-induced injury by inhibiting Fas-mediated apoptosis of cardiomyocytes (Zhao et al 2007). …”

Estresse crônico melhora a função miocárdica sem alterar a atividade do canal-L para Ca+2 em ratos

“…In addition, this variable stress for 15 days was able to produce hypertrophic cardiac and permanent cardiac structural changes 9 . Zhao et al 10 also showed that rats subjected to the chronic stress of restraint for 21 days resulted in cardiac dysfunction and to structural injury of the heart.…”