Elucidation of HDL generation mechanism in hepatocytes
| Project/Area Number |
15590952
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Nagoya City University |
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Principal Investigator |
TSUJITA Maki Nagoya City University, Graduate School of Medical Sciences, Research associates, 大学院・医学研究科, 助手 (10253262)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Shinji Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10142192)
DOHMAE Sumiko Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (70227700)
OKAZAKI Mitsuyo Tokyo Medical Dental University, College of Liberal Arts, Professor, 教養学部, 教授 (20013998)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | apolipoprotein AI / HDL generation / hepatocytes / monoclonal antibody / ABCA1 / Probucol / HepG2 cell / mouse primary hepatocytes / HDL / Hepatocyte / autocrine / 725-1E |
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| Research 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 whether endogenously synthesized or exogenously provided. Probucol, an ABCA1 inactivator, inhibited these reactions, as well as the reversible binding of apoAI to HepG2. Primary cultured hepatocytes of ABCA1-deficient mice also lacked HDL production regardless of the presenceof exogenous apoAI. HepG2 cells secreted apoAI 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 apoAI-specific monoclonal antibody, 725-1E2, was present in the culture medium, production of HDL was suppressed, whether with endogenous or exogenously added apoAI, and the antibody did not influence HDL already produced by HepG2 cells. We concluded that the main mechanism for HDL assembly by endogenous apoAl in HepG2 cells is an autocrine-like reaction in which apoAI is secreted and then interacts with cellular ABCA1 to generate HDL.
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Report
(3 results)
Research Products
(13 results)
