Orsi, Antonia, Beltrán, Belén, Clementi, Emilio, Hallén, Katarina, Feelisch, Martin and Moncada, Salvador
Continuous exposure to high concentrations of nitric oxide leads to persistent inhibition of oxygen consumption by J774 cells as well as extraction of oxygen by the extracellular medium
Biochemical Journal, 346, . (PMID:10677360).
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Nitric oxide (NO) plays a key role in many physiological and pathophysiological events, including the control of cell respiration. Both reversible and irreversible inhibition of mitochondrial respiration have been reported following the generation of NO by cells. We have exposed the murine macrophage cell line J774 to high concentrations of NO, such as are generated in some pathological conditions, and determined their effect on oxygen consumption. We observed a persistent inhibition of respiration which was due to a redox-dependent, progressive inhibition of complex I activity. No other enzyme of the respiratory chain was inhibited in this way. At the same time, we detected a paradoxical removal of oxygen by the extracellular medium. This removal was due to a chemical interaction between dissolved oxygen and NO-related species released from cells exposed to NO. A similar removal of oxygen by the cell supernatant also occurred following activation of cells with cytokines and bacterial products. Thus, the amounts of NO generated during pathological conditions may contribute to tissue hypoxia both by inhibiting cell respiration and by promoting removal of oxygen from the extracellular medium.
||cell respiration, complex I, glutathione, nitric oxide, S-nitrosation
||Clinical & Experimental Sciences
|1 March 2000||Published|
||29 Jun 2012 10:37
||17 Apr 2017 17:13
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