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脂肪酸乙酯与HepG2细胞:细胞内合成及从细胞中的释放

Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells.

作者信息

Kabakibi A, Morse C R, Laposata M

机构信息

Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA.

出版信息

J Lipid Res. 1998 Aug;39(8):1568-82.

PMID:9717716
Abstract

Fatty acid ethyl esters (FAEE), esterification products of fatty acid and ethanol, have been implicated as mediators of ethanol-induced organ damage. To understand the molecular and cellular events in FAEE synthesis and secretion, we developed a system in which HepG2 cells synthesize and release FAEE into the culture medium upon incubation with ethanol. The synthesis of FAEE was observed within 5 min of the addition of ethanol, with a plateau for FAEE synthesis after 2 h of incubation. It was also observed that FAEE are synthesized by both a microsomal FAEE synthase, which preferentially uses fatty acyl-CoA as a substrate, and a cytosolic FAEE synthase, which accepts both unesterified fatty acid and fatty acyl-CoA as substrates with a slight preference for fatty acyl-CoA. Although the kinetics of cellular FAEE synthesis await further characterization, the intracellular fatty acid substrate appears to be derived principally from glycerolipids and other esters. FAEE were released into the culture medium by a mechanism independent of the vesicular transport pathway. Lipoprotein particles and albumin were found to be carriers of FAEE after FAEE secretion from the cell.

摘要

脂肪酸乙酯(FAEE)是脂肪酸与乙醇的酯化产物,被认为是乙醇诱导器官损伤的介质。为了解FAEE合成与分泌过程中的分子和细胞事件,我们开发了一种系统,在该系统中,HepG2细胞在与乙醇孵育时会合成FAEE并释放到培养基中。在添加乙醇后5分钟内即可观察到FAEE的合成,孵育2小时后FAEE合成达到平台期。还观察到,FAEE由微粒体FAEE合酶(优先使用脂肪酰辅酶A作为底物)和胞质FAEE合酶(接受未酯化脂肪酸和脂肪酰辅酶A作为底物,对脂肪酰辅酶A略有偏好)共同合成。尽管细胞FAEE合成的动力学有待进一步表征,但细胞内脂肪酸底物似乎主要来源于甘油脂质和其他酯类。FAEE通过一种独立于囊泡运输途径的机制释放到培养基中。在FAEE从细胞分泌后,脂蛋白颗粒和白蛋白被发现是FAEE的载体。

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