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乙醇诱导肝脏线粒体结构和功能损伤的机制。

A mechanism for ethanol-induced damage to liver mitochondrial structure and function.

作者信息

Schilling R J, Reitz R C

出版信息

Biochim Biophys Acta. 1980 Dec 12;603(2):266-77. doi: 10.1016/0005-2736(80)90373-9.

DOI:10.1016/0005-2736(80)90373-9
PMID:7459353
Abstract

Mitochondria isolated from rats chronically fed ethanol demonstrated a marked inability to produce energy. The respiratory control ratio, the ADP/O ratio and state 3 respiration rates were all decreased. Coupled with other data, a progression of ethanol-induced changes is proposed with site I being altered prior to site II. Quantitation of mitochondrial cytochromes revealed decreases in cytochromes b and aa3 and an increase in c1. Evaluation of respiration activity in relation to temperature showed ethanol-induced changes in the transition temperature (Tf) which may have been related to changes in the lipid composition of the inner membrane. Mitochondrial membranes were separated, and analysis of fatty acids and phospholipids was performed. Various fatty acids were altered in both membranes; however, the outer membrane was altered more severely. A decrease in the arachidonate : linoleate ratio was observed only in the outer membrane; however, there was no ethanol-induced change in degree of unsaturation in either membrane. Phospholipid quantitation showed a reduction of total lipid phosphorous/mg protein in both membrane fractions; however, the inner membrane was most affected. Cardiolipin was the only phospholipid in this membrane which remained unaltered. The evidence indicates that the mechanism for ethanol-induced damage to the liver mitochondrion involves lipid compositional changes as well as changes in cytochromes and possibly other proteins.

摘要

从长期摄入乙醇的大鼠体内分离出的线粒体显示出明显的能量生成能力缺陷。呼吸控制率、ADP/O 比率和状态 3 呼吸速率均降低。结合其他数据,提出了乙醇诱导的变化进程,即位点 I 先于位点 II 发生改变。线粒体细胞色素的定量分析显示细胞色素 b 和 aa3 减少,而 c1 增加。对呼吸活性与温度关系的评估表明,乙醇诱导了转变温度(Tf)的变化,这可能与内膜脂质组成的变化有关。分离线粒体膜并进行脂肪酸和磷脂分析。两种膜中的各种脂肪酸均发生改变;然而,外膜的改变更为严重。仅在外膜中观察到花生四烯酸与亚油酸比率降低;然而,两种膜的不饱和度均未出现乙醇诱导的变化。磷脂定量显示两个膜组分中总脂质磷/毫克蛋白均减少;然而,内膜受影响最大。心磷脂是该膜中唯一未发生改变的磷脂。证据表明,乙醇诱导肝脏线粒体损伤的机制涉及脂质组成变化以及细胞色素和可能其他蛋白质的变化。

相似文献

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A mechanism for ethanol-induced damage to liver mitochondrial structure and function.乙醇诱导肝脏线粒体结构和功能损伤的机制。
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引用本文的文献

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Megamitochondria formation - physiology and pathology.巨型线粒体的形成——生理学与病理学
J Cell Mol Med. 2002 Oct-Dec;6(4):497-538. doi: 10.1111/j.1582-4934.2002.tb00452.x.
2
Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding.长期乙醇喂养后大鼠肝脏线粒体氧化磷酸化的动力学与调控
Biochem J. 2000 Jul 15;349(Pt 2):519-26. doi: 10.1042/0264-6021:3490519.