On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway

Maki Tsujita, Cheng Ai Wu, Sumiko Abe-Dohmae, Shinichi Usui, Mitsuyo Okazaki, Shinji Yokoyama

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalJournal of Lipid Research
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Keywords

  • ATP binding cassette transporter A1
  • Apolipoprotein A-I
  • Cholesterol
  • HepG2
  • Hepatocytes
  • High density lipoprotein
  • Probucol

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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