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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

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
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
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
1470-8728
407-412
Orsi, Antonia
658966f9-9f21-454c-bba2-04cfc0248be0
Beltrán, Belén
236a2f5b-a39f-4c30-bfb1-e3962dcc058d
Clementi, Emilio
fd06801c-677f-42a4-afa6-5b5828b120f9
Hallén, Katarina
59cecb78-9da5-4a16-b35f-e6e0cdb9f021
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750
Orsi, Antonia
658966f9-9f21-454c-bba2-04cfc0248be0
Beltrán, Belén
236a2f5b-a39f-4c30-bfb1-e3962dcc058d
Clementi, Emilio
fd06801c-677f-42a4-afa6-5b5828b120f9
Hallén, Katarina
59cecb78-9da5-4a16-b35f-e6e0cdb9f021
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Moncada, Salvador
0f661842-cd67-46e6-b82d-47f2c5e0e750

Orsi, Antonia, Beltrán, Belén, Clementi, Emilio, Hallén, Katarina, Feelisch, Martin and Moncada, Salvador (2000) 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, 407-412. (PMID:10677360)

Record type: Article

Abstract

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.

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More information

Published date: 1 March 2000
Keywords: cell respiration, complex I, glutathione, nitric oxide, S-nitrosation
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337876
URI: https://eprints.soton.ac.uk/id/eprint/337876
ISSN: 1470-8728
PURE UUID: 8211a8fc-6379-4bb1-bcca-5f181d331f32
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 29 Jun 2012 10:37
Last modified: 06 Jun 2018 12:29

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