Bolaños J P, Peuchen S, Heales S J, Land J M, Clark J B
Department of Neurochemistry, Institute of Neurology, London, England.
J Neurochem. 1994 Sep;63(3):910-6. doi: 10.1046/j.1471-4159.1994.63030910.x.
The Ca(2+)-independent form of nitric oxide synthase was induced in rat neonatal astrocytes in primary culture by incubation with lipopolysaccharide (1 microgram/ml) plus interferon-gamma (100 U/ml), and the activities of the mitochondrial respiratory chain components were assessed. Incubation for 18 h produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1 reductase (complex I) and succinate-cytochrome c reductase (complex II-III) activities were not affected. Prolonged incubation for 36 h gave rise to a 56% reduction of cytochrome c oxidase activity and a 35% reduction in succinate-cytochrome c reductase activity, but NADH-ubiquinone-1 reductase activity was unchanged. Citrate synthase activity was not affected by any of these conditions. The inhibition of the activities of these mitochondrial respiratory chain complexes was prevented by incubation in the presence of the specific nitric oxide synthase inhibitor NG-monomethyl-L-arginine. The lipopolysaccharide/interferon-gamma treatment of the astrocytes produced an increase in glycolysis and lactate formation. These results suggest that inhibition of the mitochondrial respiratory chain after induction of astrocytic nitric oxide synthase may represent a mechanism for nitric oxide-mediated neurotoxicity.
通过与脂多糖（1微克/毫升）加干扰素-γ（100单位/毫升）共同孵育，在原代培养的大鼠新生星形胶质细胞中诱导出了不依赖钙离子的一氧化氮合酶形式，并对线粒体呼吸链成分的活性进行了评估。孵育18小时导致细胞色素c氧化酶活性受到25%的抑制。NADH-泛醌-1还原酶（复合体I）和琥珀酸-细胞色素c还原酶（复合体II-III）的活性未受影响。延长孵育36小时导致细胞色素c氧化酶活性降低56%，琥珀酸-细胞色素c还原酶活性降低35%，但NADH-泛醌-1还原酶活性未变。柠檬酸合酶活性不受这些条件中任何一种的影响。在特异性一氧化氮合酶抑制剂NG-单甲基-L-精氨酸存在的情况下孵育可防止这些线粒体呼吸链复合体活性受到抑制。脂多糖/干扰素-γ对星形胶质细胞的处理导致糖酵解和乳酸生成增加。这些结果表明，星形胶质细胞一氧化氮合酶诱导后线粒体呼吸链受到抑制可能是一氧化氮介导的神经毒性的一种机制。
