Differential effects of bcl-2 on cell death triggered under ATP-depleting conditions.
The intracellular ATP concentration decides on the onset of either apoptosis or necrosis in Jurkat cells exposed to death stimuli. Bcl-2 can block apoptotic demise, which occurs preferably under conditions of high cellular ATP levels. Here, we investigated the effects of Bcl-2 on the necrotic type of cell demise that prevails under conditions of energy loss. ATP levels were modulated by using mitochondrial inhibitors, such as rotenone or S-nitrosoglutathione, in medium either lacking glucose or supplemented with glucose to stimulate glycolytic ATP generation. Under conditions of ATP depletion, staurosporine (STS) induced >90% necrosis in vector control-transfected cells, whereas bcl-2-transfected cells were protected. Thus, the antiapoptotic protein Bcl-2 can reduce the overall amount of cell death in ATP-depleted cells regardless whether it occurs by apoptosis or necrosis. Cytochrome c release, normally preceding STS-induced necrosis, was also inhibited by Bcl-2. However, Bcl-2 did not prevent an initial STS-induced drop of the mitochondrial membrane potential (DeltaPsi(m)). Therefore, the mechanisms whereby Bcl-2 prevents cell death and favors retention of cytochrome c in the mitochondria require neither the maintenance of mitochondrial DeltaPsi nor the maintenance of normal ATP levels.
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Faculty of Biology, University of Konstanz, Konstanz, D-78457, Germany.
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Nicotera
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D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis; D003574:Cytochrome c Group / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012402:Rotenone / Q000494:pharmacology; D026422:S-Nitrosoglutathione; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
D003574:Cytochrome c Group; D009603:Nitroso Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D012402:Rotenone; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D000255:Adenosine Triphosphate; D005978:Glutathione; D019311:Staurosporine