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

FEBS Lett. 1999 Nov 19;461(3):306-10. doi: 10.1016/s0014-5793(99)01486-6.


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 degrees C, Hsp72 and Hsp27 were not induced above 42 degrees C. Moreover, cells underwent apoptosis at 44 degrees C and necrosis at 46 degrees 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 degrees C failed to restore Hsp induction despite inhibition of heat-induced apoptosis. Furthermore, accumulation of Hsps after incubation at 42 degrees 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / genetics
  • Caspases / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Heat-Shock Proteins / physiology*
  • Hot Temperature*
  • Humans
  • Jurkat Cells
  • Kinetics
  • Mitochondria / physiology
  • Stress, Physiological / genetics
  • Stress, Physiological / physiopathology*


  • Heat-Shock Proteins
  • Caspases