title: Thermotolerance and cell death are distinct cellular responses to stress: dependence on heat shock proteins.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden. afshin.samali@imm.ki.se
authors.forename: A
authors.initials: A
authors.lastname: Samali
authors.forename: C I
authors.initials: CI
authors.lastname: Holmberg
authors.forename: L
authors.initials: L
authors.lastname: Sistonen
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
mesh_terms: D017209:Apoptosis / Q000235:genetics; D020169:Caspases / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008928:Mitochondria / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology*
chemical_list: D006360:Heat-Shock Proteins; D020169:Caspases