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乙醇与生物膜:损伤与适应

Ethanol and biological membranes: injury and adaptation.

作者信息

Rubin E, Rottenberg H

出版信息

Pharmacol Biochem Behav. 1983;18 Suppl 1:7-13. doi: 10.1016/0091-3057(83)90139-9.

Abstract

Ethanol intoxication affects the protein and lipid constituents of biological membranes. Mitochondria exhibit specific decreases in components of the electron transport chain and in protein synthesis. In vitro ethanol reduces the transition temperatures of membrane-bound enzyme activities and decreases the order parameter. On the other hand, both are increased after chronic ethanol administration. After chronic ethanol treatment membranes are resistant to disordering by ethanol, possibly owing to an increased saturation of mitochondrial phospholipids, particularly cardiolipin. The increased rigidity of mitochondrial and synaptosomal membranes is associated with reduced binding of ethanol and of the general anesthetic halothane. The data suggest that initially ethanol increases the fluidity of all biological membranes. If continued chronically, this effect is balanced by a change in the lipid composition of the membranes, which increases their rigidity and makes them resistant to disordering by ethanol (homeoviscous adaptation). The change in molecular order reduces the binding of ethanol and other compounds, but also impairs a variety of membrane-bound functions. These changes may play a role in tolerance to ethanol and cross-tolerance to anesthetics, and in the pathogenesis of maladies associated with alcohol abuse.

摘要

乙醇中毒会影响生物膜的蛋白质和脂质成分。线粒体在电子传递链的成分和蛋白质合成方面表现出特定的减少。体外实验中,乙醇会降低膜结合酶活性的转变温度并降低有序参数。另一方面,长期给予乙醇后,这两者都会增加。长期乙醇处理后,膜对乙醇引起的无序状态具有抗性,这可能是由于线粒体磷脂(特别是心磷脂)饱和度增加所致。线粒体膜和突触体膜刚性的增加与乙醇和全身麻醉剂氟烷的结合减少有关。数据表明,最初乙醇会增加所有生物膜的流动性。如果长期持续,这种效应会被膜脂质组成的变化所平衡,这种变化会增加膜的刚性并使其对乙醇引起的无序状态具有抗性(等黏滞适应)。分子有序性的变化会减少乙醇和其他化合物的结合,但也会损害多种膜结合功能。这些变化可能在对乙醇的耐受性和对麻醉剂的交叉耐受性以及与酒精滥用相关疾病的发病机制中起作用。

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