Comparison of the protective activities generated by two survival proteins: Bcl-2 and Hsp27 in L929 murine fibroblasts exposed to menadione or staurosporine.
Hsp27 and Bcl-2 are survival proteins that protect against cell death. We have compared the specific protective activity (protection per number of molecules expressed) mediated by these proteins when they are expressed in L929 murine fibroblasts. We found that Hsp27 and Bcl-2 efficiently delayed the cytotoxicity generated by menadione. Both proteins interfered with the mitochondria membrane potential collapse, the reactive oxygen species (ROS) burst and the decrease in glutathione level induced by this oxidant. In untreated cells, both proteins decreased the ROS levels and raised the glutathione cellular content. Taking their levels of expression into account, we concluded that Bcl-2 was much more active than Hsp27 for counteracting the above-mentioned menadione effects, and for modulating the ROS and glutathione levels in untreated cells. Both Hsp27 and Bcl-2 also conferred cellular resistance to staurosporine, a kinase inhibitor that induces apoptosis without generating an oxidative stress. In this case, Bcl-2 was again much more active than Hsp27. Fractionation studies indicated that, in L929 cells, Hsp27 is essentially present in the cytosol while Bcl-2 is membrane and mitochondria-associated. Hence, despite some similar cellular effects resulting from their expression, Bcl2 and Hsp27 polypeptides protect against oxidative stress and apoptosis with different efficiencies and by using different mechanisms.
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Equipe stress oxydant, chaperons et apoptose. Centre de Génétique Moléculaire et Cellulaire, CNRS UMR-5534, Université Claude Bernard LYON-I, 69622, Villeurbanne, France.
Arrigo
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D000818:Animals; D017209:Apoptosis; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000502:physiology*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D019311:Staurosporine / Q000633:toxicity*; D014812:Vitamin K / Q000633:toxicity*
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014812:Vitamin K; D019311:Staurosporine