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oxHDL 通过 PPARγ 和 p38 MAP 激酶依赖的机制降低人巨噬细胞上 CD36 的表达。

oxHDL decreases the expression of CD36 on human macrophages through PPARgamma and p38 MAP kinase dependent mechanisms.

机构信息

Department of cardiology, Peking University People's Hospital, Beijing, China.

出版信息

Mol Cell Biochem. 2010 Sep;342(1-2):171-81. doi: 10.1007/s11010-010-0481-y. Epub 2010 May 11.

Abstract

CD36, belongs to class B scavenger receptor family, is a macrophage receptor for oxidized low-density lipoprotein (oxLDL) and has been proven to play a critical role in atherosclerotic foam cell formation. In addition, CD36 expression is regulated by many factors including oxLDL and HDL. A recent study suggests that CD36 can also bind with oxidized high-density lipoprotein (oxHDL). However, the direct role of oxHDL in atherosclerosis is still not clear and it is not known whether oxHDL has any influence on the expression of CD36 in macrophages. Here, we performed experiments to investigate the effect of oxHDL on the expression of CD36 on human peripheral blood monocytes-macrophages and the possible mechanisms. Our results suggest that the uptake of oxHDL by CD36 on macrophages accelerates foam cell formation. In addition, oxHDL can down-regulate both the mRNA and surface protein expression of CD36 on human peripheral macrophages in vitro. oxHDL increased the mRNA expression and protein phosphorylation of peroxisome proliferators-activated receptor-gamma (PPARgamma). Using different mitogen-activated protein kinase (MAPK) inhibitors, we demonstrated that oxHDL regulated CD36 and PPARgamma expression in a p38-MAP kinase dependent mechanism.

摘要

CD36 属于 B 类清道夫受体家族,是氧化型低密度脂蛋白(oxLDL)的巨噬细胞受体,已被证明在动脉粥样硬化泡沫细胞形成中起关键作用。此外,CD36 的表达受许多因素的调节,包括 oxLDL 和 HDL。最近的一项研究表明,CD36 还可以与氧化型高密度脂蛋白(oxHDL)结合。然而,oxHDL 在动脉粥样硬化中的直接作用尚不清楚,也不知道 oxHDL 是否对巨噬细胞中 CD36 的表达有任何影响。在这里,我们进行了实验来研究 oxHDL 对人外周血单核细胞-巨噬细胞中 CD36 表达的影响及其可能的机制。我们的结果表明,oxHDL 通过巨噬细胞上的 CD36 摄取加速了泡沫细胞的形成。此外,oxHDL 可以在体外下调人外周巨噬细胞中 CD36 的 mRNA 和表面蛋白表达。oxHDL 增加了过氧化物酶体增殖物激活受体-γ(PPARγ)的 mRNA 表达和蛋白磷酸化。使用不同的丝裂原活化蛋白激酶(MAPK)抑制剂,我们证明 oxHDL 通过 p38-MAP 激酶依赖机制调节 CD36 和 PPARγ 的表达。

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