Rotenone and pyruvate prevent the tert-butylhydroperoxide-induced necrosis of U937 cells and allow them to proliferate.
Exposure of U937 cells to tert-butylhydroperoxide (tB-OOH) led to cyclosporin A-sensitive mitochondrial membrane permeability transition and necrosis. Pyruvate and rotenone, which increase mitochondrial NADH via different mechanisms, prevented these responses and the cells which received these treatments proliferated with kinetics similar to those observed in untreated cells. In contrast with these results, cells rescued by cyclosporin A were unable to proliferate. Thus, mitochondrial NADH plays a pivotal role in preventing upstream events which result in the onset of mitochondrial membrane permeability transition and death in cells exposed to tB-OOH. These events appear to be critical for recovery of the ability of the cells to proliferate.
Sestili
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Instituto di Farmacologia e Farmacognosia, Università di Urbino, Italy.
Brambilla
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Cantoni
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D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival; D016572:Cyclosporine / Q000494:pharmacology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009336:Necrosis; D019289:Pyruvic Acid / Q000494:pharmacology*; D012402:Rotenone / Q000494:pharmacology*; D013997:Time Factors; D020298:U937 Cells; D014475:Uncoupling Agents / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; D012402:Rotenone; D016572:Cyclosporine; D019289:Pyruvic Acid; D020122:tert-Butylhydroperoxide