EFFECT OF EXOGENOUS AND ENDOGENOUS NITRIC-OXIDE ON MITOCHONDRIAL RESPIRATION OF RAT HEPATOCYTES
EFFECT OF EXOGENOUS AND ENDOGENOUS NITRIC-OXIDE ON MITOCHONDRIAL RESPIRATION OF RAT HEPATOCYTES
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DOI：
10.1152/ajpcell.1991.260.5.c910
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发表时间：
1991-05-01
影响因子：
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通讯作者：
SIMMONS, RL
中科院分区：
文献类型：
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作者：
STADLER, J;BILLIAR, TR;SIMMONS, RL
虽然一氧化氮（.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。 HC短时间暴露于真实的N = O导致线粒体顺乌头酸酶、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物I和II）的浓度依赖性抑制。 最易受.N = O抑制的是线粒体顺乌头酸酶，其中观察到酶活性降低至对照的20.2 +/- 1.6%。 与线粒体顺乌头酸酶相反，胞浆顺乌头酸酶活性不受N = O的抑制。 在暴露于最大抑制浓度.N = O后，线粒体顺乌头酸酶活性在6 h内完全恢复。 复合物I在此潜伏期内没有完全恢复。 内源性N = O生物合成诱导HC细胞因子和脂多糖的特定组合。 与这些刺激物孵育18小时后，检测到线粒体顺乌头酸酶活性显著抑制至对照组的70.8 +/- 2.4%。 然而，这只是部分地由于.N = O的作用。 线粒体功能的非N = O依赖性抑制似乎由肿瘤坏死因子介导。
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.