On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway
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DOI：
10.1194/jlr.m400402-jlr200
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发表时间：
2005-01-01
影响因子：
6.5
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
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作者：
Tsujita, M;Wu, CA;Yokoyama, S
在肝细胞中研究了ABCA1和螺旋载脂蛋白与细胞脂质组装HDL的机制。HepG2细胞和小鼠原代培养的肝细胞都产生含有载脂蛋白A-I （apoA-I）的HDL，无论是内源性合成还是外源性提供。Probucol是一种ABCA1灭活剂，可以抑制这些反应以及apoA-I与HepG2的可逆结合。无论外源性apoA-I是否存在，abca1缺陷小鼠的原代培养肝细胞也缺乏HDL的产生。即使probucol使ABCA1失活，HepG2细胞也会向培养基中分泌apoa - 1，但由于HDL的产生受到抑制，apoa - 1仍以游离形式存在。当培养基中存在无脂apoa -1特异性单克隆抗体725-1E2时，无论是内源性还是外源性添加apoa -1，都能抑制HDL的产生，并且该抗体不影响HepG2细胞已经产生的HDL。我们得出结论，内源性apoA-I在HepG2细胞中组装HDL的主要机制是一种类似自分泌的反应，apoA-I分泌后与细胞ABCA1相互作用生成HDL。
The mechanism for the assembly of HDL with cellular lipid by ABCA1 and helical apolipoprotein was investigated in hepatocytes. Both HepG2 cells and mouse primary culture hepatocytes produced HDL with apolipoprotein A-I (apoA-I) whether endogenously synthesized or exogenously provided. Probucol, an ABCA1 inactivator, inhibited these reactions, as well as the reversible binding of apoA-I to HepG2. Primary cultured hepatocytes of ABCA1-deficient mice also lacked HDL production regardless of the presence of exogenous apoA-I. HepG2 cells secreted apoA-I into the medium even when ABCA1 was inactivated by probucol, but it was all in a free form as HDL production was inhibited. When a lipid-free apoA-I-specific monoclonal antibody, 725-1E2, was present in the culture medium, production of HDL was suppressed, whether with endogenous or exogenously added apoA-I, and the antibody did not influence HDL already produced by HepG2 cells. We conclude that the main mechanism for HDL assembly by endogenous apoA-I in HepG2 cells is an autocrine-like reaction in which apoA-I is secreted and then interacts with cellular ABCA1 to generate HDL.