Hasaba A, Laposata M
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Alcohol Clin Exp Res. 2001 Mar;25(3):338-43.
Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by the esterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma after ethanol ingestion bind to lipoproteins and albumin.
In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid to generate 3H-FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE acceptors.
The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium.
These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage.
脂肪酸乙酯(FAEEs)是脂肪酸与乙醇酯化反应产生的乙醇非氧化代谢产物。FAEEs在体内和体外均被认为是乙醇诱导器官损伤的介质。乙醇摄入后,它们可在血液和许多器官中被检测到,基于此,它们是活体患者以及尸检对象乙醇摄入量的有用标志物。乙醇摄入后在人血浆中发现的FAEEs与脂蛋白和白蛋白结合。
在本研究中,我们使用肝癌细胞模型(HepG2)来确定脂蛋白或白蛋白是否刺激HepG2细胞合成和/或分泌FAEEs。由于已证明FAEEs会降低HepG2细胞的增殖和蛋白质合成,将它们从细胞中去除可能会恢复正常细胞活性。将HepG2细胞与100 mM乙醇和6 nM 3H油酸一起孵育,以在细胞内生成3H-FAEEs。使用低密度脂蛋白、高密度脂蛋白和白蛋白作为FAEE受体进行剂量反应和时间进程研究。
结果表明,这些FAEE载体中的每一种都能有效提取FAEEs,并且向细胞外培养基中添加FAEE载体也会刺激FAEE的合成。
这些观察结果表明,脂蛋白和白蛋白可以从HepG2细胞中提取乙酯,从而可能限制酒精性肝损伤。