Elucidation of HDL generation mechanism in hepatocytes

肝细胞HDL生成机制的阐明

• 批准号: 15590952
• 负责人: TSUJITA Maki
• 金额: $ 2.24万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590952/
• 关键词: apolipoprotein AI; HDL generation; hepatocytes; monoclonal antibody; ABCA1; Probucol; HepG2 cell; mouse primary hepatocytes; HDL; Hepatocyte; autocrine; 725-1E

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.

在肝细胞中研究了ABCA 1和螺旋载脂蛋白组装HDL与细胞脂质的机制。HepG 2细胞和小鼠原代培养肝细胞产生HDL和载脂蛋白A-I，无论是内源性合成还是外源性提供。普罗布考，ABCA 1灭活剂，抑制这些反应，以及apoAI的HepG 2的可逆结合。ABCA 1缺陷小鼠的原代培养肝细胞也缺乏HDL的产生，无论是否存在外源性apoAI。HepG 2细胞分泌apoAI到培养基中，即使ABCA 1被普罗布考灭活，但它都是在一个自由的形式，因为HDL的生产受到抑制。当无脂质的apoAI特异性单克隆抗体725- 1 E2存在于培养基中时，HDL的产生被抑制，无论是内源性还是外源性添加的apoAI，并且抗体不影响已经由HepG 2细胞产生的HDL。我们的结论是，HDL组装的主要机制由内源性apoAl在HepG 2细胞是一个自分泌样反应，其中apoAI分泌，然后与细胞ABCA 1相互作用，以产生HDL。

项目成果

Potential involvement of dissociated apolipoprotein A-I in the ABCA1-dependent cellular lipid release by high density lipoprotein.

解离载脂蛋白 A-I 可能参与高密度脂蛋白依赖于 ABCA1 的细胞脂质释放。

• 发表时间: 2004
• 期刊: J Lipid Res. 45(4)
• 作者: Okuhira K;Tsujita M;Yamauchi Y;Abe-Dohmae S;Kato K;Handa T;Yokoyama S.
• 通讯作者: Yokoyama S.

An Inhibitor of acylCoA : cholesterol acyltransferase increases expression of ABC-binding cassett transporter AI and thereby enhances the ApoAI-mediated release of cholesterol from macrophages

酰基辅酶 A 抑制剂：胆固醇酰基转移酶可增加 ABC 结合盒转运蛋白 AI 的表达，从而增强 ApoAI 介导的巨噬细胞胆固醇释放

• 发表时间: 2004
• 期刊: Biochemica et Biophysica Acta 1636
• 作者: 杉本佳奈美;辻田麻紀;呉成愛;鈴木和夫;横山信治
• 通讯作者: 横山信治

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

• DOI: 10.1194/jlr.m400402-jlr200
• 发表时间: 2005-01-01
• 期刊: JOURNAL OF LIPID RESEARCH
• 影响因子: 6.5
• 作者: Tsujita, M;Wu, CA;Yokoyama, S
• 通讯作者: Yokoyama, S

Isoosmotic Isolation of Rat Brain Synaptic Vesicles, Some of Which contain Tyrosine Hydroxylase

大鼠脑突触小泡的等渗分离，其中一些突触小泡含有酪氨酸羟化酶

• 发表时间: 2004
• 期刊: Journal of Biochemistry 136
• 作者: 都築紀宏;辻田麻紀
• 通讯作者: 辻田麻紀

An inhibitor of acylCoA: cholesterol acyltransferase increases expression of ATP-binding cassette transporter A1 and thereby enhances the ApoA-I-mediated release of cholesterol from macrophages.

酰基辅酶 A：胆固醇酰基转移酶的抑制剂可增加 ATP 结合盒转运蛋白 A1 的表达，从而增强 ApoA-I 介导的巨噬细胞胆固醇释放。

• 发表时间: 2004
• 期刊: Biochim Biophys Acta. 1636(1)
• 作者: Sugimoto K;Tsujita M;Wu CA;Suzuki K;Yokoyama S.
• 通讯作者: Yokoyama S.