Stadler J, Billiar T R, Curran R D, Stuehr D J, Ochoa J B, Simmons R L
Department of Surgery, University of Pittsburgh, Pennsylvania 15261.
Am J Physiol. 1991 May;260(5 Pt 1):C910-6. doi: 10.1152/ajpcell.1991.260.5.C910.
Although nitric oxide (.N = O) biosynthesis is inducible in rat hepatocytes (HC), the physiological significance of .N = O production by these cells is unknown. Short exposure of HC to authentic .N = O led to a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubiquinone oxidoreductase (complexes I and II of the mitochondrial electron transport chain). Most susceptible to .N = O inhibition was mitochondrial aconitase, in which a reduction in enzyme activity to 20.2 +/- 1.6% of control was observed. In contrast to mitochondrial aconitase, cytosolic aconitase activity was not inhibited by .N = O. After exposure to a maximal inhibitory concentration of .N = O, mitochondrial aconitase activity recovered completely within 6 h. Complex I did not fully recover within this incubation period. Endogenous .N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide. After 18 h of incubation with these stimuli, a significant inhibition of mitochondrial aconitase activity to 70.8 +/- 2.4% of controls was detected. However, this was due only in part to the action of .N = O. A non- .N = O-dependent inhibition of mitochondrial function appeared to be mediated by tumor necrosis factor.
尽管一氧化氮（·N = O）的生物合成在大鼠肝细胞（HC）中是可诱导的，但这些细胞产生·N = O的生理意义尚不清楚。将HC短暂暴露于纯·N = O会导致线粒体乌头酸酶、NADH - 泛醌氧化还原酶和琥珀酸 - 泛醌氧化还原酶（线粒体电子传递链的复合体I和II）受到浓度依赖性抑制。对·N = O抑制最敏感的是线粒体乌头酸酶，观察到其酶活性降至对照的20.2±1.6%。与线粒体乌头酸酶相反，胞质乌头酸酶活性不受·N = O抑制。在暴露于最大抑制浓度的·N = O后，线粒体乌头酸酶活性在6小时内完全恢复。复合体I在该孵育期内未完全恢复。细胞因子和脂多糖的特定组合可诱导HC内源性·N = O的生物合成。在用这些刺激物孵育18小时后，检测到线粒体乌头酸酶活性显著抑制至对照的70.8±2.4%。然而，这仅部分归因于·N = O的作用。线粒体功能的非·N = O依赖性抑制似乎是由肿瘤坏死因子介导的。
