Interferon‐γ and Tumor Necrosis Factor Synergize to Induce Nitric Oxide Production and Inhibit Mitochondrial Respiration in Vascular Smooth Muscle Cells
作者:
Yong-jian Geng,
Göran Hansson,
Elisabeth Holme,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 71,
issue 5
页码: 1268-1276
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: interferon gamma;mitochondria;nitric oxide;vascular smooth muscle;tumor necrosis factor
数据来源: OVID
摘要:
Nitric oxide (NO) is an important signal substance in cell-cell communication and can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells (SMCs). NO is synthesized from L-arginine by the enzyme NO synthase, which is present in endothelial cells. It was recently shown that SMCs may themselves produce NO or an NO-related compound. We have studied NO production and its effects on energy metabolism in cultured rat aortic smooth muscle cells. It was observed that the cytokines, interferon-γ and tumor necrosis factor-ar, synergistically induced an arginine-dependent production of NO in these cells. This was associated with an inhibition of complex I (NADH: ubiquinone oxidoreductase) and complex II (succinate: ubiquinone oxidoreductase) activities of the mitochondrial respiratory chain, suggesting that NO blocks mitochondrial respiration in these cells. Lactate accumulated in the media of the cells, implying an increased anaerobic glycolysis, but there was no reduction of viability. An NO-dependent inhibition of mitochondrial respiration and a switch to anaerobic glycolysis would reduce the energy production of the SMCs. This would in turn reduce the contractile capacity of the cell and might represent another NO-dependent vasodilatory mechanism. It could be of particular importance in inflammation, since cytokines released by inflammatory cells may induce autocrine NO production in SMCs.
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