Stadler J, Curran R D, Ochoa J B, Harbrecht B G, Hoffman R A, Simmons R L, Billiar T R
Department of Surgery, University of Pittsburgh, PA 15261.
Arch Surg. 1991 Feb;126(2):186-91. doi: 10.1001/archsurg.1991.01410260074010.
Nitric oxide, a highly reactive radical, was recently identified as an intermediate of L-arginine metabolism in mammalian cells. We have shown that nitric oxide synthesis is induced in vitro in cultured hepatocytes by supernatants from activated Kupffer cells or in vivo by injecting rats with nonviable Corynebacterium parvum. In both cases, nitric oxide biosynthesis in hepatocytes was associated with suppression of total protein synthesis. This study attempts to determine the effect of nitric oxide biosynthesis on the activity of specific hepatocytic mitochondrial enzymes and to determine whether inhibition of protein synthesis is caused by suppression of energy metabolism. Exposure of hepatocytes to supernatants from activated Kupffer cells led to a 30% decrease of aconitase (Krebs cycle) and complex I (mitochondrial electron transport chain) activity. Using NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, we demonstrated that the inhibition of mitochondrial aconitase activity was due, in part, to the action of nitric oxide. In contrast, in vivo nitric oxide synthesis of hepatocytes from Corynebacterium parvum-treated animals had no effect on mitochondrial respiration. This suggests that inhibition of protein synthesis by nitric oxide is not likely to be mediated by inhibition of energy metabolism.
一氧化氮是一种高反应性自由基，最近被确定为哺乳动物细胞中L-精氨酸代谢的中间产物。我们已经表明，在体外，培养的肝细胞中一氧化氮的合成可由活化的库普弗细胞的上清液诱导，在体内，可通过给大鼠注射无活力的微小棒状杆菌诱导。在这两种情况下，肝细胞中一氧化氮的生物合成均与总蛋白质合成的抑制有关。本研究试图确定一氧化氮生物合成对特定肝细胞线粒体酶活性的影响，并确定蛋白质合成的抑制是否由能量代谢的抑制引起。将肝细胞暴露于活化的库普弗细胞的上清液中会导致乌头酸酶（三羧酸循环）和复合体I（线粒体电子传递链）活性降低30%。使用一氧化氮合成抑制剂NG-单甲基-L-精氨酸，我们证明线粒体乌头酸酶活性的抑制部分归因于一氧化氮的作用。相反，用微小棒状杆菌处理的动物肝细胞的体内一氧化氮合成对线粒体呼吸没有影响。这表明一氧化氮对蛋白质合成的抑制不太可能由能量代谢的抑制介导。
