EFFECTS OF ETHANOL ON HEPATIC PROTEIN TRAFFICKING - IMPAIRMENT OF RECEPTOR-MEDIATED ENDOCYTOSIS
EFFECTS OF ETHANOL ON HEPATIC PROTEIN TRAFFICKING - IMPAIRMENT OF RECEPTOR-MEDIATED ENDOCYTOSIS
复制标题
DOI：
10.1093/oxfordjournals.alcalc.a044986
复制
发表时间：
1990-01-01
影响因子：
2.8
通讯作者：
SORRELL, MF
中科院分区：
文献类型：
--
作者：
TUMA, DJ;CASEY, CA;SORRELL, MF
酒精摄入会扰乱蛋白质在肝脏中的运输。在酒精处理的动物的肝脏中，蛋白质分泌和质膜组装途径被证明是受损的；然而，沿着受体介导的内吞途径的交通似乎特别容易受到乙醇的影响。使用去唾液酸糖蛋白作为研究受体介导的内吞作用的模型配体，我们已经确定了这一多步骤途径中至少有三个步骤受到乙醇处理的影响。这些改变的步骤是受体的循环，受体-配体复合体的内在化，以及内体中配体与其受体的解离。酒精引起的内吞紊乱在酒精性肝损伤开始和主导的小静脉周围区域比在肝脏的门静脉周围区域更严重。此外，最近的研究表明，乙醇处理也会改变其他配体的内吞作用，包括表皮生长因子和胰岛素。已提出的解释错误内吞作用的机制包括：乙醛与微管蛋白的加合物导致微管功能受损，内小体不正确的酸化和包被小孔中有缺陷的受体聚集。由于受体介导的肝脏内吞作用是调节各种激素、生长因子和其他配体水平的重要过程，而且由于内吞作用也可能是引起各种配体的生物学效应的一个完整过程，这一重要过程的变化可能会扰乱肝脏和整个生物体的众多代谢和动态平衡事件。
Ethanol administration disorders protein trafficking in the liver. The protein secretory and plasma membrane assembly pathways have been shown to be impaired in the liver of ethanol-treated animals; however, traffic along the receptor-mediated endocytosis pathway appears to be especially susceptible to alterations by ethanol. Using asialoglycoproteins as model ligands for studying receptor-mediated endocytosis, we have identified at least three steps of this multi-step pathway that are affected by ethanol treatment. These altered steps are recycling of the receptor, internalization of the receptor-ligand complex and dissociation of the ligand from its receptor in endosomes. Ethanol-induced derangements of endocytosis are more severe in the perivenule region, where alcoholic liver injury starts and predominates, than in the periportal region of the liver. In addition, recent studies have shown that the endocytosis of other ligands, including epidermal growth factor and insulin, are also altered by ethanol treatment. Mechanisms which have been proposed to explain faulty endocytosis include: acetaldehyde adducts to tubulin resulting in impaired microtubule function, improper acidification of endosomes and defective receptor clustering in coated pits. Since receptor-mediated endocytosis by the liver represents an important process by which levels of various hormones, growth factors and other ligands are regulated, and since endocytosis may also be an integral process by which the biological effects of various ligands are elicited, changes in this important process could disrupt numerous metabolic and homeostatic events in the liver and total organism.