Casey C A, Wiegert R L, Tuma D J
Liver Study Unit, V.A. Medical Center, Omaha, NE.
Biochem Biophys Res Commun. 1993 Sep 15;195(2):1127-33. doi: 10.1006/bbrc.1993.2161.
Ethanol administration has been shown to alter various protein trafficking pathways in the liver, including protein secretion, plasma membrane assembly and receptor-mediated endocytosis. Molecules such as proteins are transported into and within the cells via endosomal vesicles, and acidification of these endosomes appears to be critical for efficient sorting and trafficking of proteins. In the present study we examined whether ethanol administration impaired the ATP-dependent acidification of endosomes. Liver endosomes were prepared from rats after intravenous labeling with fluorescently labeled ligands and the initial pH and extent of ATP-dependent acidification was determined. Our results showed that the intrinsic pH was significantly higher and that the ATP-dependent acidification of the interior of the endosomes was inhibited in ethanol-fed versus control animals. This impairment of endosomal acidification may play a role in the impaired protein trafficking which occurs as a result of ethanol administration.
已证实，给予乙醇会改变肝脏中各种蛋白质运输途径，包括蛋白质分泌、质膜组装和受体介导的内吞作用。蛋白质等分子通过内体囊泡转运进入细胞并在细胞内运输，而这些内体的酸化似乎对蛋白质的有效分选和运输至关重要。在本研究中，我们检测了给予乙醇是否会损害内体的ATP依赖性酸化。在用荧光标记配体进行静脉注射标记后，从大鼠制备肝脏内体，并测定初始pH值和ATP依赖性酸化程度。我们的结果表明，与对照动物相比，乙醇喂养动物的内体固有pH值显著更高，并且内体内部的ATP依赖性酸化受到抑制。内体酸化的这种损害可能在因给予乙醇而发生的蛋白质运输受损中起作用。
