Volentine G D, Tuma D J, Sorrell M F
Gastroenterology. 1986 Jan;90(1):158-65. doi: 10.1016/0016-5085(86)90088-0.
Ethanol administration inhibits the secretion of proteins by the liver, resulting in their hepatocellular retention. Experiments were designed in this study to determine the subcellular location of the retained secretory proteins. Ethanol was administered acutely to nonfasted rats by gastric intubation, whereas control animals received an isocaloric dose of glucose. Two hours after intubation, when maximum blood ethanol levels (45 mM) were observed, [3H]leucine and [14C]fucose were injected simultaneously into the dorsal vein of the penis. The labelling of secretory proteins was determined in the liver and plasma at various time periods after label injection. Ethanol treatment decreased the secretion of both leucine- and fucose-labeled proteins into the plasma. This inhibition of secretion was accompanied by a corresponding increase in the hepatic retention of both leucine- and fucose-labeled immunoprecipitable secretory proteins. At the time of maximum inhibition of secretion, leucine labeled secretory proteins located in the Golgi apparatus represented about 50% of the accumulated secretory proteins in the livers of the ethanol-treated rats, whereas the remainder was essentially equally divided among the rough and smooth endoplasmic reticulum and cytosol. Because fucose is incorporated into secretory proteins almost exclusively in the Golgi complex, fucose-labeled proteins accumulated in the livers of the ethanol-treated rats mainly in the Golgi apparatus, with the remainder located in the cytosol. These results show that ethanol administration causes an impaired movement of secretory proteins along the secretory pathway, and that secretory proteins accumulate mainly, but not exclusively, in the Golgi apparatus.
给予乙醇会抑制肝脏蛋白质的分泌，导致其在肝细胞内潴留。本研究设计了实验来确定潴留的分泌蛋白在亚细胞水平的定位。通过胃管向非禁食大鼠急性给予乙醇，而对照动物给予等热量的葡萄糖。插管后两小时，当观察到血液乙醇水平达到最高值（45 mM）时，将[3H]亮氨酸和[14C]岩藻糖同时注入阴茎背静脉。在注射标记物后的不同时间段，测定肝脏和血浆中分泌蛋白的标记情况。乙醇处理降低了亮氨酸和岩藻糖标记蛋白向血浆中的分泌。这种分泌抑制伴随着亮氨酸和岩藻糖标记的可免疫沉淀分泌蛋白在肝脏中潴留的相应增加。在分泌抑制达到最大值时，位于乙醇处理大鼠肝脏高尔基体中的亮氨酸标记分泌蛋白约占累积分泌蛋白的50%，而其余部分基本平均分布在粗面和滑面内质网以及细胞质中。由于岩藻糖几乎只在高尔基体复合物中掺入分泌蛋白，因此岩藻糖标记蛋白在乙醇处理大鼠肝脏中主要积聚在高尔基体中，其余部分位于细胞质中。这些结果表明，给予乙醇会导致分泌蛋白沿分泌途径的转运受损，并且分泌蛋白主要但并非仅积聚在高尔基体中。
