On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway
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 A...
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doaj-7811d01eba7d4a50b95859f46cb9c7d02021-04-27T04:46:41ZengElsevierJournal of Lipid Research0022-22752005-01-01461154162On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathwayMaki Tsujita0Cheng-Ai Wu1Sumiko Abe-Dohmae2Shinichi Usui3Mitsuyo Okazaki4Shinji Yokoyama5Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanBiochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanBiochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanBiochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanBiochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanBiochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan; Faculty of Health Sciences, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan; Laboratory of Chemistry, College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa 272-0827, JapanThe 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.http://www.sciencedirect.com/science/article/pii/S0022227520340918cholesterolhigh density lipoproteinhepatocytesHepG2probucolapolipoprotein A-I |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maki Tsujita Cheng-Ai Wu Sumiko Abe-Dohmae Shinichi Usui Mitsuyo Okazaki Shinji Yokoyama |
spellingShingle |
Maki Tsujita Cheng-Ai Wu Sumiko Abe-Dohmae Shinichi Usui Mitsuyo Okazaki Shinji Yokoyama On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway Journal of Lipid Research cholesterol high density lipoprotein hepatocytes HepG2 probucol apolipoprotein A-I |
author_facet |
Maki Tsujita Cheng-Ai Wu Sumiko Abe-Dohmae Shinichi Usui Mitsuyo Okazaki Shinji Yokoyama |
author_sort |
Maki Tsujita |
title |
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway |
title_short |
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway |
title_full |
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway |
title_fullStr |
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway |
title_full_unstemmed |
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway |
title_sort |
on the hepatic mechanism of hdl assembly by the abca1/apoa-i pathway |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2005-01-01 |
description |
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. |
topic |
cholesterol high density lipoprotein hepatocytes HepG2 probucol apolipoprotein A-I |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520340918 |
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