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.