Sorrell M F, Nauss J M, Donohue T M, Tuma D J
Gastroenterology. 1983 Mar;84(3):580-6.
The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [14C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [14C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [14C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration.
在大鼠肝切片中研究了长期给予乙醇对蛋白质和糖蛋白合成及分泌的影响。与配对喂养的对照组相比，给予乙醇4 - 5周的大鼠的肝切片将[14C]葡糖胺掺入培养基中三氯乙酸可沉淀蛋白的能力降低；然而，慢性乙醇处理并未影响肝细胞糖蛋白的标记。用抗大鼠血清蛋白的抗血清对放射性标记的分泌性（血清）糖蛋白进行免疫沉淀，结果显示，在给予乙醇的大鼠的肝切片培养基中，葡糖胺标记蛋白的出现也受到类似的显著抑制。然而，细胞内分泌性糖蛋白的标记受到的影响最小。通过测量[14C]亮氨酸掺入培养基和肝蛋白中来确定蛋白质合成，结果显示，与配对喂养的对照组相比，给予乙醇的大鼠的肝切片中蛋白质合成减少。总蛋白以及可免疫沉淀的分泌蛋白均是如此，尽管保留在肝切片中的分泌蛋白的标记减少程度低于总的放射性标记肝蛋白。当使用末端糖[14C]岩藻糖作为前体，以便更密切地关注肝糖蛋白分泌的最后步骤时，从长期给予乙醇的大鼠获得的肝切片显示，岩藻糖标记蛋白向培养基中的分泌受损。当将乙醇（5或10 mM）添加到含有来自给予乙醇的大鼠的肝切片的孵育培养基中时，慢性乙醇处理引起的蛋白质和糖蛋白合成及分泌的改变会进一步增强。本研究结果表明，从长期给予乙醇的大鼠制备的肝切片表现出蛋白质和糖蛋白合成及分泌受损，并且急性给予乙醇会进一步加剧这些缺陷。
