7-酮基胆固醇-9-羧基壬酸通过 CD36 增强 ATP 结合盒转运蛋白 A1 的表达。
7-Ketocholesteryl-9-carboxynonanoate enhances the expression of ATP-binding cassette transporter A1 via CD36.
机构信息
College of Life Science and Technology, Key Laboratory of Carbohydrate and Lipid Metabolism Research, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Liaoning 116622, China.
出版信息
Atherosclerosis. 2013 Jan;226(1):102-9. doi: 10.1016/j.atherosclerosis.2012.10.038. Epub 2012 Nov 6.
BACKGROUND
CD36 signal transductions have been reported by a variety of lipid moiety of oxidized low-density lipoprotein (oxLDL), however, CD36 signal induced by 7-ketocholesteryl-9-carboxynonanoate (oxLig-1), a lipid moiety of oxLDL has not been elucidated.
METHODS AND RESULTS
OxLig-1 leads to activation and recruitment of Src kinase Fyn, Lyn and caveolin-1 to CD36 in J774A.1 cells, but not in CD36 knockdown cells. The mitogen-activated protein (MAP) kinases c-Jun N-terminal kinase 2 (JNK2) and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) are specifically phosphorylated in J774A.1 cells after treatment with oxLig-1 and inhibited by pretreatment of Src inhibitor, AG1879. The expression of ABCA1 is up-regulated by treatment with oxLig-1in J774A.1 cells, and the increased expression of ABCA1 is dramatically down-regulated by pretreatment with pharmacological inhibitors of ERK (PD98059) and JNK (SP600125).
CONCLUSIONS
The specific CD36 signal induced by oxLig-1 initiated the activation of Fyn, Lyn, caveolin-1, JNK2 and ERK1/2, and resulted in the up-regulation of ABCA1.
背景
已报道 CD36 信号转导由多种氧化型低密度脂蛋白（oxLDL）的脂质部分引发，然而，oxLDL 的脂质部分 7-酮胆固醇-9-羧基壬酸酯（oxLig-1）诱导的 CD36 信号尚未阐明。
方法和结果
oxLig-1 导致 Src 激酶 Fyn、Lyn 和 caveolin-1 在 J774A.1 细胞中而不是在 CD36 敲低细胞中向 CD36 的激活和募集。促分裂原激活的蛋白（MAP）激酶 c-Jun N-末端激酶 2（JNK2）和细胞外信号调节蛋白激酶 1 和 2（ERK1/2）在 J774A.1 细胞中经 oxLig-1 处理后特异性磷酸化，并被 Src 抑制剂 AG1879 预处理抑制。oxLig-1 处理可上调 J774A.1 细胞中 ABCA1 的表达，而 ERK（PD98059）和 JNK（SP600125）的药理学抑制剂预处理可显著下调 ABCA1 的表达增加。
结论
oxLig-1 诱导的特异性 CD36 信号启动了 Fyn、Lyn、caveolin-1、JNK2 和 ERK1/2 的激活，导致 ABCA1 的上调。
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