Thermotolerance and cell death are distinct cellular responses to stress: Dependence on heat shock proteins

We tested the hypothesis that heat shock protein (Hsp) induction and cell death are mutually exclusive responses to stress. Despite activation of heat shock transcription factor 1 at temperatures ranging from 40 to 46°C, Hsp72 and Hsp27 were not induced above 42°C. Moreover, cells underwent apoptosis at 44°C and necrosis at 46°C, with mitochondrial cytochrome c release at both temperatures. However, only apoptosis was associated with caspase activation. Treatment of cells with z-VAD-fmk prior to heat shock at 44°C failed to restore Hsp induction despite inhibition of heat-induced apoptosis. Furthermore, accumulation of Hsps after incubation at 42°C rendered the cells resistant to apoptosis. These results suggest that lack of Hsp induction is the cause rather than the consequence of cell death. Copyright (C) 1999 Federation of European Biochemical Societies.