EFFECT OF CHRONIC ETHANOL FEEDING ON GLUTATHIONE AND FUNCTIONAL INTEGRITY OF MITOCHONDRIA IN PERIPORTAL AND PERIVENOUS RAT HEPATOCYTES
EFFECT OF CHRONIC ETHANOL FEEDING ON GLUTATHIONE AND FUNCTIONAL INTEGRITY OF MITOCHONDRIA IN PERIPORTAL AND PERIVENOUS RAT HEPATOCYTES
复制标题
DOI：
10.1172/jci117306
复制
发表时间：
1994-07-01
影响因子：
15.9
通讯作者：
FERNANDEZCHECA, JC
中科院分区：
文献类型：
--
作者：
GARCIARUIZ, C;MORALES, A;FERNANDEZCHECA, JC
慢性乙醇喂养选择性地损害细胞质谷胱甘肽转运到线粒体基质。由于乙醇诱导的肝细胞损伤优先定位于小叶中央区域，我们检测了乙醇喂养大鼠线粒体GSH运输的肝腺泡分布。我们制备了对饲大鼠和乙醇喂养大鼠的富含门静脉周围（PP）和静脉周围（PV）的肝细胞，并从这些细胞中提取线粒体。以每10(6)个细胞或每微升线粒体基质体积表示，乙醇喂养大鼠的PP细胞和PV细胞中GSH的线粒体池大小均减少。在PP细胞和PV细胞中，线粒体GSH的再积累率以及线粒体与细胞质GSH的线性关系都较低，在PV细胞中观察到的影响更为明显。PP和PV乙醇喂养的大鼠线粒体功能完整性较低，这与细胞ATP水平和线粒体膜电位下降有关，PV细胞的影响更大。乙醇摄食导致的线粒体GSH耗竭先于线粒体功能改变的发生，这表明线粒体GSH对于维持细胞器的功能能力至关重要，PV细胞中乙醇摄食导致的线粒体GSH耗竭可能与酒精性肝病的发病机制有关。
Chronic ethanol feeding selectively impairs the translocation of cytosol GSH into the mitochondrial matrix. Since ethanol-induced liver cell injury is preferentially localized in the centrilobular area, we examined the hepatic acinar distribution of mitochondrial GSH transport in ethanol-fed rats. Enriched periportal (PP) and perivenous (PV) hepatocytes from pair- and ethanol-fed rats a ere prepared as well as mitochondria from these cells. The mitochondrial pool size of GSH was decreased in both PP and PV cells from ethanol-fed rats either as expressed per 10(6) cells or per microliter of mitochondrial matrix volume. The rate of reaccumulation of mitochondrial GSH and the linear relationship of mitochondrial to cytosol GSH from ethanol-fed mitochondria were lower for both PP and PV cells, effects observed more prominently in the PV cells. Mitochondrial functional integrity was lower in both PP and PV ethanol-fed rats, which was associated with decreased cellular ATP levels and mitochondrial membrane potential, effects which were greater in the PV cells. Mitochondrial GSH depletion by ethanol feeding preceded the onset of functional changes in mitochondria, suggesting that mitochondrial GSH is critical in maintaining a functionally competent organelle and that the greater depletion of mitochondrial GSH by ethanol feeding in PV cells could contribute to the pathogenesis of alcoholic liver disease.