Mild thermotolerance induced at 40 degrees C protects HeLa cells against activation of death receptor-mediated apoptosis by hydrogen peroxide

作者：Pallepati Pragathi; Averill Bates Diana A

来源：Free Radical Biology and Medicine, 2011, 50(6): 667-679.

DOI：10.1016/j.freeradbiomed.2010.11.022

• Oxidative stress
• Hydrogen peroxide
• Apoptosis
• Thermotolerance
• Adaptive response
• Death receptor
• p53 protein
• Caspase
• Heat-shock protein
• Antioxidant
• Free radicals

Preexposure to mild temperatures such as 40 degrees C induces thermotolerance, whereby cells resist subsequent exposure to a toxic insult. This study investigates the protective effect of mild thermotolerance (3 h, 40 degrees C) against activation of death receptor-mediated apoptosis by H(2)O(2) in HeLa cells. H(2)O(2) (5-50 mu M) caused rapid activation (1-3 h) of the Fas death receptor pathway of apoptosis, which was evident by up-regulation of the death ligand FasL and recruitment of the adaptor protein Fas-associated death domain to the plasma membrane. This resulted in activation of caspase-8 and caspase-2, which led to activation of the cross-talk pathway involving Bid cleavage, t-Bid translocation to mitochondria, and caspase-9 activation. These changes were all diminished in thermotolerant cells. Mild thermotolerance also protected cells against cytotoxicity from H(2)O(2) as well as execution-phase events of apoptosis such as caspase-3 activation and chromatin condensation. The antioxidant polyethylene glycol-catalase abolished FasL induction and caspase-8 activation due to H(2)O(2) FasL up-regulation; activation of caspases-8, -2, -9, and -3: and chromatin condensation were decreased by the p53 inhibitor pifithrin-alpha, implicating p53 as an upstream factor in the activation of death receptor-mediated apoptosis by H(2)O(2). This study advances knowledge about the protective effect of adaptive responses induced by mild stresses, such as fever temperatures, against induction of apoptosis by oxidative stress.

• 出版日期2011-3-15