Heat shock protein 70 inhibits caspase-dependent and -independent apoptosis in Jurkat T cells

Heat shock protein 70 (hsp70) is a stress-inducible protein that prevents a poptosis induced by a wide range of cytotoxic agents by an as yet undefined mechanism. The caspase family of cysteine proteases have been attributed a central role in the execution of apoptosis. However, several cases of casp ase-independent apoptosis have been recently reported, suggesting that casp ases may not be necessary for apoptosis in all cells. This study examines t he protective role of hsp70 in both caspase-dependent and -independent apop tosis. Hydrogen peroxide (H2O2) used at low and high concentrations in Jurk at T cells induces caspase-dependent and -independent apoptosis, respective ly. A hsp70-transfected Jurkat clone was used to observe the protection med iated by hsp70 during these two forms of apoptosis. Results reveal that hsp 70 inhibits: both caspase-dependent and -independent apoptosis. Furthermore , measurement of caspase-3 activity during caspase-dependent apoptosis reve aled that caspase activation was inhibited in hsp70 transfectants. Early ap optotic events, such as mitochondrial depolarization, cytochrome c release, and increased intracellular calcium, were demonstrated to be common to bot h caspase-dependent and -independent H2O2-induced apoptosis. The inhibition of these events by hsp70 suggests that hsp70 may be an important anti-apop totic regulator, functioning at a very early stage in the apoptotic pathway . (C) 2000 Academic Press.