FEEDING S-ADENOSYL-L-METHIONINE ATTENUATES BOTH ETHANOL-INDUCED DEPLETION OF MITOCHONDRIAL GLUTATHIONE AND MITOCHONDRIAL DYSFUNCTION IN PERIPORTAL AND PERIVENOUS RAT HEPATOCYTES
FEEDING S-ADENOSYL-L-METHIONINE ATTENUATES BOTH ETHANOL-INDUCED DEPLETION OF MITOCHONDRIAL GLUTATHIONE AND MITOCHONDRIAL DYSFUNCTION IN PERIPORTAL AND PERIVENOUS RAT HEPATOCYTES
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DOI：
10.1016/0270-9139(95)90430-1
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发表时间：
1995-01-01
期刊：
影响因子：
13.5
通讯作者：
FERNANDEZCHECA, JC
中科院分区：
文献类型：
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作者：
GARCIARUIZ, C;MORALES, A;FERNANDEZCHECA, JC
线粒体谷胱甘肽在维持细胞器的功能上发挥着重要作用。先前的研究表明，乙醇喂养选择性地耗尽线粒体谷胱甘肽池，尤其是来自静脉周围肝细胞的线粒体。由于 S-腺苷-L-蛋氨酸 (SAM) 是谷胱甘肽前体并维持生物膜的结构和功能，本研究的目的是确定 SAM 对长期乙醇喂养大鼠的谷胱甘肽以及静脉周围 (PV) 和门脉周围 (PP) 线粒体功能的影响。 SAM 给药导致配对饲喂组或乙醇饲喂组的 PP 和 PV 细胞中基础细胞质和线粒体谷胱甘肽显着增加。当补充有 SAM 的乙醇喂养大鼠的肝细胞与蛋氨酸加丝氨酸或 N-乙酰半胱氨酸一起孵育时，线粒体谷胱甘肽与胞质溶胶平行增加，而在没有 SAM 的乙醇喂养大鼠的细胞中未观察到这种效应。饲喂等摩尔的 N-乙酰半胱氨酸会升高胞质谷胱甘肽，但不能防止线粒体谷胱甘肽缺陷。此外，SAM 喂养导致 PP 和 PV 线粒体的细胞三磷酸腺苷 (ATP) 水平（23% 至 43%）、线粒体膜电位（17% 至 25%）和呼吸解偶联控制比 (UCR)（分别从 5.1 +/- 0.7 至 7.3 +/- 0.6 和 2.1 +/- 0.3 至 6.1 +/- 0.7）显着保持。因此，SAM 的这些作用表明，它可能是一种有用的药物，可以通过维持线粒体谷胱甘肽转运来保护酒精中毒引起的肝病中受损的线粒体完整性。
Mitochondrial glutathione plays an important role in maintaining a functionally competent organelle. Previous studies have shown that ethanol feeding selectively depletes the mitochondrial glutathione pool, more predominantly in mitochondria from perivenous hepatocytes. Because S-adenosyl-L-methionine (SAM) is a glutathione precursor and maintains the structure and function of biological membranes, the purpose of the present study was to determine the effects of SAM on glutathione and function of perivenous (PV) and periportal (PP) mitochondria from chronic ethanol-fed rats. SAM administration resulted in a significant increase in the basal cytosol and mitochondrial glutathione in both PP and PV cells from both pair-fed or ethanol-fed groups. When hepatocytes from ethanol-fed rats supplemented with SAM were incubated with methionine plus serine or N-acetylcysteine, mitochondrial glutathione increased in parallel with cytosol, an effect not observed in cells from ethanol-fed rats without SAM. Feeding equimolar N-acetylcysteine raised cytosol glutathione but did not prevent the mitochondrial glutathione defect. In addition, SAM feeding resulted in significant preservation of cellular adenosine triphosphate (ATP) levels (23% to 43%), mitochondrial membrane potential (17% to 25%), and the uncoupler control ratio (UCR) of respiration (from 5.1 +/- 0.7 to 7.3 +/- 0.6 and 2.1 +/- 0.3 to 6.1 +/- 0.7) for PP and PV mitochondria, respectively. Thus, these effects of SAM suggest that it may be a useful agent to preserve the disturbed mitochondrial integrity in liver disease caused by alcoholism through maintenance of mitochondrial glutathione transport.