Cardellach F, Taraschi T F, Ellingson J S, Stubbs C D, Rubin E, Hoek J B
Department of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107.
Biochem J. 1991 Mar 1;274 ( Pt 2)(Pt 2):565-73. doi: 10.1042/bj2740565.
The effect of long-term ethanol intake on the structural and functional characteristics of rat skeletal-muscle mitochondria and sarcoplasmic reticulum was investigated. Functionally, skeletal-muscle mitochondria were characterized by a high respiratory control index and ADP/O ratio and a high State-3 respiration rate with different substrates. These parameters were not significantly different in preparations from control and ethanol-fed rats, except for a small increase in the rate of oxidation of alpha-oxoglutarate/malate in the latter. In submitochondrial particles from the two groups of animals there was no significant difference in cytochrome content, ATPase activity or the activity of respiratory-chain complexes. Mitochondrial membranes from untreated and ethanol-fed rats showed no difference in the baseline e.s.r. order parameter, and both preparations were equally sensitive to disordering by ethanol in vitro. Similarly, sarcoplasmic-reticulum preparations were not significantly affected by long-term ethanol feeding with respect to Ca2(+)-ATPase activity or in baseline order parameter and susceptibility to membrane disordering by ethanol in vitro. These membranes were also equally sensitive to degradation by exogenous phospholipase A2. Ethanol feeding did not alter the class composition of mitochondrial or sarcoplasmic-reticulum membrane phospholipids, nor the acyl composition of individual phospholipid classes. Specifically, the changes in acyl composition that characteristically occur in liver microsomal phosphatidylinositol and liver mitochondrial cardiolipin were not observed in the corresponding phospholipids from skeletal-muscle membranes. In experiments where membrane preparations from liver and skeletal muscle from the same ethanol-fed animals were compared, the liver membranes developed membrane tolerance, with the muscle membranes retaining normal sensitivity to disordering effects by ethanol. It is concluded that: (a) different tissues from the same animals differ in their susceptibility to ethanol; (b) the tissue-specific lack of development of membrane tolerance correlates with a lack of chemical changes in the phospholipids and with a retention of normal function of mitochondria and sarcoplasmic reticulum; (c) effects of chronic ethanol intake on muscle function are not due to a defect in the mitochondrial energy supply.
研究了长期摄入乙醇对大鼠骨骼肌线粒体和肌浆网结构与功能特性的影响。在功能方面，骨骼肌线粒体的特征是具有较高的呼吸控制指数和ADP/O比率，以及使用不同底物时较高的状态3呼吸速率。除了乙醇喂养组中α-酮戊二酸/苹果酸氧化速率略有增加外，对照组和乙醇喂养大鼠的制备物中的这些参数没有显著差异。两组动物的亚线粒体颗粒中，细胞色素含量、ATP酶活性或呼吸链复合物活性均无显著差异。未处理和乙醇喂养大鼠的线粒体膜在基线电子自旋共振有序参数上没有差异，并且两种制备物在体外对乙醇引起的无序状态同样敏感。同样，长期乙醇喂养对肌浆网制备物的Ca2(+)-ATP酶活性、基线有序参数以及体外对乙醇引起的膜无序状态的敏感性没有显著影响。这些膜对外源磷脂酶A2的降解也同样敏感。乙醇喂养并未改变线粒体或肌浆网膜磷脂的类别组成，也未改变各个磷脂类别的酰基组成。具体而言，在骨骼肌膜的相应磷脂中未观察到肝脏微粒体磷脂酰肌醇和肝脏线粒体心磷脂中特有的酰基组成变化。在比较来自同一乙醇喂养动物的肝脏和骨骼肌膜制备物的实验中，肝脏膜产生了膜耐受性，而肌肉膜对乙醇的无序作用保持正常敏感性。得出以下结论：(a) 同一动物的不同组织对乙醇的敏感性不同；(b) 组织特异性的膜耐受性缺乏与磷脂的化学变化缺乏以及线粒体和肌浆网的正常功能保留相关；(c) 慢性乙醇摄入对肌肉功能的影响不是由于线粒体能量供应缺陷所致。
