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The effect of nitricoxide on cellrespiration: A key tounderstanding itsrole in cell survivalor death Belén BeltránAnthony MathurMichael R. Duchen2000 год

The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death
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Аннотация: The mitochondrion is a key organelle in the control of cell death. Nitric oxide (NO) inhibits complex IV in the respiratory chain and is reported to possess both proapoptotic and antiapoptotic actions. We investigated the effects of continuous inhibition of respiration by NO on mitochondrial energy status and cell viability. Serum-deprived human T cell leukemia (Jurkat) cells were exposed to NO at a concentration that caused continuous and complete (∼85%) inhibition of respiration. Serum deprivation caused progressive loss of mitochondrial membrane potential (Δψ m ) and apoptotic cell death. In the presence of NO, Δψ m was maintained compared to controls, and cells were protected from apoptosis. Similar results were obtained by using staurosporin as the apoptotic stimulus. As exposure of serum-deprived cells to NO progressed (>5 h), however, Δψ m fell, correlating with the appearance of early apoptotic features and a decrease in cell viability. Glucose deprivation or iodoacetate treatment of cells in the presence of NO resulted in a collapse of Δψ m , demonstrating involvement of glycolytic ATP in its maintenance. Under these conditions cell viability also was decreased. Treatment with oligomycin and/or bongkrekic acid indicated that the maintenance of Δψ m during exposure to NO is caused by reversal of the ATP synthase and other electrogenic pumps. Thus, blockade of complex IV by NO initiates a protective action in the mitochondrion to maintain Δψ m ; this results in prevention of apoptosis. It is likely that during cellular stress involving increased generation of NO this compound will trigger a similar sequence of events, depending on its concentration and duration of release.
Год издания: 2000
Авторы: Belén Beltrán, Anthony Mathur, Michael R. Duchen, Jorge D. Erusalimsky, Salvador Moncada
Издательство: National Academy of Sciences
Источник: Proceedings of the National Academy of Sciences
Ключевые слова: Cell death mechanisms and regulation, ATP Synthase and ATPases Research, Mitochondrial Function and Pathology
Другие ссылки: Proceedings of the National Academy of Sciences (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)