Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver.
Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver.
复制标题
长期乙醇给药对灌注大鼠肝脏摄取和降解脱唾液酸糖蛋白的影响。
DOI：
10.1016/0006-2952(90)90501-b
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发表时间：
1990
影响因子：
5.8
通讯作者：
Tuma,DJ
中科院分区：
文献类型：
--
作者：
Casey,CA;Volentine,GD;Jankovich,CJ;Kragskow,SL;Tuma,DJ
我们先前已经发现，在酒精喂养4-6周的大鼠肝细胞对125I-ASOR的受体介导的内吞作用(RME)过程中，125I-ASOR的结合、内化、降解和受体配体解离减少。在本研究中，我们以完整的肝脏灌流为模型，研究了乙醇喂养对RME的影响。雄性Spraogue-Dawley大鼠被喂以含有乙醇(36%卡路里)或等卡路里碳水化合物的流食。然后在灌流的一段时间内检测受体介导的125I-ASOR的内吞作用。在所有情况下，标记的糖蛋白清除后，在介质中出现较慢但稳定的酸溶产物。与对照组动物相比，饮用乙醇的动物从循环灌流液中清除标记配体的速度显著减慢(P<；0.01)。在这个模型中，酒精喂养的动物的ASOR表面结合和降解的损害也被证明。当我们检查不同灌流时间后标记配体的亚细胞分布时，我们发现在对照肝脏中，放射性标记的配体从含有内体和质膜的亚细胞部分转移到含有溶酶体的部分，而显著减少了配体转移到乙醇处理的溶酶体的部分。这些结果表明，在离体肝灌流模型中，乙醇给药抑制了ASOR的RME，从而证实了我们早先报道的离体肝细胞的缺陷。此外，细胞内RME途径上的配体运输也被乙醇处理所改变，这表现为ASOR从内体到溶酶体室的移动受损。
We have shown previously reduced binding, internalization, degradation and receptorligand dissociation during receptor-mediated endocytosis (RME) of125I-asialoorosomucoid (ASOR) by hepatocytes isolated from rats fed ethanol for 4–6 weeks. In the present study, we investigated the effect of ethanol feeding on RME by using the intact perfused liver as a model. Male, Sprague-Dawley rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric carbohydrate. Receptor-mediated endocytosis of125I-ASOR was then examined over a time course of perfusion. In all cases, clearance of the labeled glycoprotein was followed by a slower but steady appearance of acid-soluble products in the medium. Ethanol-fed animals had a significantly (P< 0.01) slower rate of clearance of the labeled ligand from the circulating perfusate than did control animals. Impairment of ASOR surface binding and degradation in ethanol-fed animals was also demonstrated in this model. When we examined the subcellular distribution of labeled ligand after various times of perfusion, we found that in control livers, a shift of radiolabeled ligand from the subcellular fractions containing endosomes and plasma membranes to fractions containing lysosomes occurred, while significantly less ligand was shifted to the lysosomes of ethanol-treated rats. These results show that ethanol administration inhibits RME of ASOR in the isolated perfused liver model, thus confirming our earlier reported defects in isolated hepatocytes. In addition, transport of ligand along the intracellular RME pathway was also shown to be altered by ethanol treatment as indicated by the impaired movement of ASOR from the endosomal to the lysosomal compartment.