Seenaiah B, Bichenkov E, Ellingson J S
Department of Pathology, Anatomy, and Cell Biology, Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Alcohol Clin Exp Res. 1998 Sep;22(6):1245-54.
The purpose of our study was to determine whether chronic ethanol consumption affected membrane assembly by altering the formation of specific molecular species of phosphatidylethanolamine (PE) and their subsequent incorporation into the plasma membrane (PM). We investigated the effects on the PE species made by the two major pathways in hepatocytes: (1) from CDP-ethanolamine in the endoplasmic reticulum, and (2) by the decarboxylation of phosphatidylserine (PS) in the mitochondria. Ethanol consumption exerted significant effects on the formation of ethanolamine-derived PE species and affected mainly two species, the 16:0/22:6 and 18:0/20:4 species. In cultured hepatocytes from ethanol-fed rats labeled with [3H]ethanolamine for 0.25 to 4 hr, the amount of the [3H]16:0/22:6 PE species was decreased compared with that in control cells, whereas the amount of [3H]18:0/20:4 species was increased. The amount of the [3H]16:0/22:6 PE species on the cell surface was also decreased in hepatocytes from ethanol-fed rats, whereas the amount of [3H]18:0/20:4 species was increased. In contrast, the profile of [3H]PE species formed in cells treated with [3H]serine exhibited minor alterations, and the profile of the serine-derived [3H]PE species on the cells surface was not altered after 4 hr of labeling. The changes in ethanolamine-derived species were apparently caused by time-dependent alterations in the metabolic processes, because the presence of 110 mM ethanol in the culture media did not affect the profiles of [3H]PE species in cells from control or ethanol-fed rats and was not required to sustain the altered profiles. The results indicate that the synthesis of specific PE molecular species and their appearance on the PM may occur by compartmentalized processes which are distinguishable by different sensitivities to ethanol consumption. The results indicate that ethanol consumption may contribute alcoholic hepatic injury by interfering with the metabolism of specific PE molecular species and their assembly into the PM.
我们研究的目的是确定长期乙醇摄入是否通过改变磷脂酰乙醇胺（PE）特定分子种类的形成及其随后整合到质膜（PM）中而影响膜组装。我们研究了对肝细胞中两条主要途径产生的PE种类的影响：（1）在内质网中由CDP - 乙醇胺产生，以及（2）在线粒体中由磷脂酰丝氨酸（PS）脱羧产生。乙醇摄入对乙醇胺衍生的PE种类的形成产生显著影响，主要影响两种种类，即16:0/22:6和18:0/20:4种类。在用[3H]乙醇胺标记0.25至4小时的乙醇喂养大鼠的培养肝细胞中，[3H]16:0/22:6 PE种类的量与对照细胞相比减少，而[3H]18:0/20:4种类的量增加。乙醇喂养大鼠的肝细胞中细胞表面的[3H]16:0/22:6 PE种类的量也减少，而[3H]18:0/20:4种类的量增加。相比之下，用[3H]丝氨酸处理的细胞中形成的[3H]PE种类的谱显示出轻微变化，并且在标记4小时后细胞表面丝氨酸衍生的[3H]PE种类的谱没有改变。乙醇胺衍生种类的变化显然是由代谢过程中随时间的改变引起的，因为培养基中110 mM乙醇的存在不影响对照或乙醇喂养大鼠细胞中[3H]PE种类的谱，并且维持改变的谱也不需要乙醇。结果表明，特定PE分子种类的合成及其在质膜上的出现可能通过不同的过程发生，这些过程对乙醇摄入的敏感性不同。结果表明，乙醇摄入可能通过干扰特定PE分子种类的代谢及其组装到质膜中而导致酒精性肝损伤。
