Thermotolerance induced at a mild temperature of 40 degrees C protects cells against heat shock-induced apoptosis.
Apoptosis constitutes a response of organisms to various physiological or pathological stimuli, and to different stresses. The ability of thermotolerance induced at a mild temperature of 40 degrees C to protect against activation of the apoptotic cascade by heat shock was investigated. When Chinese hamster ovary and human adenocarcinoma cervical cells were pretreated at 40 degrees C for 3 h, they were resistant to subsequent lethal heat shock at 43 degrees C. Induction of thermotolerance at 40 degrees C led to increased expression of heat shock proteins 27, 32, 72, and 90. Heat shock induced apoptotic events at the mitochondrial level, involving a decrease in membrane potential, translocation of Bax to mitochondria, and liberation of cytochrome c into the cytosol. These events were diminished in thermotolerant cells. Heat shock (42-45 degrees C) caused activation of initiator caspase-9 and effector caspases-3, -6, and -7, relative to controls at 37 degrees C. Activation of caspases was decreased in thermotolerant cells. Heat shock caused fragmentation of the caspase substrate, inhibitor of caspase-activated DNase. Fragmentation was diminished in thermotolerant cells. Thermotolerance afforded protection against heat shock-induced nuclear chromatin condensation, but not against necrosis.
Bettaieb
Ahmed
A
Département de chimie-biochimie and TOXEN, Université du Québec à Montréal, Succursale Centre Ville, Montréal, Québec, Canada.
Averill-Bates
Diana A
DA
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000235:genetics; D006224:Cricetinae; D045304:Cytochromes c / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013696:Temperature; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D002843:Chromatin; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases