Oxidized Low-Density Lipoprotein Inhibits THP-1-Derived Macrophage Autophagy via TET2 Down-regulation
Oxidized Low-Density Lipoprotein Inhibits THP-1-Derived Macrophage Autophagy via TET2 Down-regulation
复制标题
氧化低密度脂蛋白通过 TET2 下调抑制 THP-1 衍生的巨噬细胞自噬
DOI：
10.1007/s11745-014-3977-5
复制
发表时间：
2015-02-01
期刊：
影响因子：
1.9
通讯作者：
Wei, Dangheng
中科院分区：
文献类型：
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作者：
Li, Guohua;Peng, Juan;Wei, Dangheng
氧化低密度脂蛋白（ox-LDL）是动脉粥样硬化的独立危险因素。然而，其促动脉粥样硬化作用的机制尚未得到很好的探讨。DNA去甲基化修饰是通过DNA甲基转移酶或泰特家族对多种生物学和病理学过程进行的一种危机性表观遗传调控。本研究旨在探讨ox-LDL对巨噬细胞自噬的影响及其可能的表观遗传学机制。结果显示，0、10、20、40和80 mg/L ox-LDL处理24 h后，自噬标志物Beclin 1和LC 3的蛋白水平表达明显降低（P< 0.05）。TET 2 mRNA和蛋白表达明显降低（P< 0.05）。TET 2siRNA预处理后，Beclin 1和LC 3的mRNA和蛋白水平较80 mg/L处理组降低（P<0. 01）。预处理组Beclin 1和LC 3-II的mRNA和蛋白水平在DNA甲基转移酶抑制剂5-氮杂-2 ′-脱氧胞苷（5-aza-2′-deoxycytidine）作用下明显上调（P< 0.05）。与Western blot结果一致，细胞免疫荧光显示TET 2 siRNA组LC 3-II蛋白浓度降低，而5-aza-2′-deoxycytidine组LC 3-II蛋白浓度升高。这些结果表明DNA去甲基化修饰调节ox-LDL处理的THP-1巨噬细胞的自噬，TET 2可能是一种新的调节因子。
Oxidized low-density lipoprotein (ox-LDL) is an independent risk factor of atherosclerosis. However, the mechanism underlying its pro-atherosclerosis roles has not yet been well explored. DNA demethylation modification, via DNA methyltransferases or ten-eleven-translocation (TET) family, is a crisis epigenetic regulation for various biological and pathological processes. This study aimed to investigate the effects of ox-LDL on macrophage autophagy and its potential epigenetic mechanism. Results showed that after treatment with 0, 10, 20, 40 or 80 mg/L ox-LDL for 24 h, the autophagy markersBeclin 1andLC3expression were obviously decreased at protein levels (P< 0.05). The mRNA and protein expression ofTET2was evidently decreased (P< 0.05). After pre-treatment withTET2siRNA, the mRNA and protein levels ofBeclin 1andLC3decreased compared with the 80 mg/L treatment group (P< 0.01). The mRNA and protein levels ofBeclin 1and LC3-II were up-regulated (P< 0.05) in the 5-aza-2′-deoxycytidine (a DNA methyltransferase inhibitor) of pretreatment group. Consistent with the Western blot results, cell immunofluorescence showed that the protein concentration of LC3-II decreased in theTET2siRNA group and increased in the 5-aza-2′-deoxycytidine group. Taken together, these results showed that DNA demethylation modifications regulate ox-LDL-treated THP-1 macrophages autophagy andTET2might be a novel regulator.