Transcellular regulation of cell respiration by nitric oxide generated by activated macrophages

FEBS Letters

Moncada, Salvador¹  Foxwell, Neale¹  Brown, Guy C² 

[1] The Wolfson Institute for Biomedical Research, University College London, Tottenham Court Road, London W1P 9LN, UK;Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK

关键词: Nitric oxide;    Macrophage;    Mitochondrion;    Mitochondrial respiration;    Inflammation;    Cytotoxicity;    DMEM;    Dulbecco's modified Eagle medium;    FCCP;    carbonyl cyanide p-trifluoromethoxyphenylhydrazone;    HEPES;    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;    iNOS;    inducible form of nitric oxide synthase;    NMMA;    NG-monomethyl-l-arginine;    ODQ;    1H-[1;    2;    4]oxadiazolo[4;    3-a] quinoxaline-1-one;    TMPD;    N;    N;    N 1 N 1-tetramethyl-p-phenylene diamine;   

DOI  :  10.1016/S0014-5793(98)01404-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A macrophage cell line (J774), activated with interferon-γ and endotoxin to express the inducible form of NO synthase (iNOS), immediately inhibited the cellular respiration of co-incubated L-929 fibroblasts or non-activated J774 macrophages. The inhibition was potent, rapid and reversible when the NO was removed by adding oxyhaemoglobin or by inhibiting iNOS. Exogenously added NO also rapidly and reversibly inhibited cellular respiration over the same range of NO concentrations. This inhibition was competitive with oxygen and due to direct inhibition of cytochrome oxidase. Thus, NO generated by one cell can regulate the respiration of adjacent cells, supporting the hypothesis that NO may be a physiological and/or pathological regulator of cellular respiration, via its inhibition of cytochrome oxidase.

【 授权许可】

Unknown