Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells A POTENTIAL ROLE FOR REDUCING LIPID ACCUMULATION
Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells A POTENTIAL ROLE FOR REDUCING LIPID ACCUMULATION
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DOI：
10.1074/jbc.m113.477505
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发表时间：
2013-08-02
影响因子：
4.8
通讯作者：
Kim, Jeong-a
中科院分区：
文献类型：
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作者：
Kim, Hae-Suk;Montana, Vedrana;Kim, Jeong-a
表没食子儿茶素没食子酸酯 (EGCG) 是绿茶中的主要多酚，对预防心血管疾病具有有益作用。自噬是一种保护细胞免受应激条件影响的细胞过程。为了确定 EGCG 的有益作用是否是由涉及自噬的机制介导的，研究了 EGCG 刺激的自噬在异位脂质积累中的作用。 EGCG 处理增加了原代牛主动脉内皮细胞 (BAEC) 中 LC3-II 和自噬体的形成。 EGCG 诱导的 LC3-II 形成需要钙调蛋白依赖性蛋白激酶激酶 β 的激活，事实证明，钙调蛋白依赖性蛋白激酶激酶 β 的敲低会显着损害 EGCG 诱导的 LC3-II 形成。这种效应很可能是由于胞质 Ca2+ 负载所致。为了确定 EGCG 是否影响棕榈酸酯诱导的脂质积累，检查了 EGCG 对自噬流以及脂滴和自噬溶酶体共定位的影响。 EGCG 使棕榈酸盐引起的自噬流损伤正常化。 EGCG 显着减少了棕榈酸酯引起的脂滴积累。阻断自噬体降解与 EGCG 在异位脂质积累中的作用相反，表明 EGCG 的作用是通过自噬体降解实现的。其机制可能是由于脂滴和自噬溶酶体的共定位增加。与单独用棕榈酸酯处理的细胞相比，用 EGCG 和棕榈酸酯处理细胞时，脂滴与 LC3 和溶酶体的共定位显着增加。总的来说，这些发现表明 EGCG 通过促进自噬流调节异位脂质积累，并进一步表明 EGCG 可能是预防心血管并发症的潜在治疗剂。
Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in the prevention of cardiovascular disease. Autophagy is a cellular process that protects cells from stressful conditions. To determine whether the beneficial effect of EGCG is mediated by a mechanism involving autophagy, the roles of the EGCG-stimulated autophagy in the context of ectopic lipid accumulation were investigated. Treatment with EGCG increased formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (BAEC). Activation of calmodulin-dependent protein kinase kinase beta was required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation was significantly impaired by knockdown of calmodulin-dependent protein kinase kinase beta. This effect is most likely due to cytosolic Ca2+ load. To determine whether EGCG affects palmitate-induced lipid accumulation, the effects of EGCG on autophagic flux and co-localization of lipid droplets and autophagolysosomes were examined. EGCG normalized the palmitate-induced impairment of autophagic flux. Accumulation of lipid droplets by palmitate was markedly reduced by EGCG. Blocking autophagosomal degradation opposed the effect of EGCG in ectopic lipid accumulation, suggesting the action of EGCG is through autophagosomal degradation. The mechanism for this could be due to the increased co-localization of lipid droplets and autophagolysosomes. Co-localization of lipid droplets with LC3 and lysosome was dramatically increased when the cells were treated with EGCG and palmitate compared with the cells treated with palmitate alone. Collectively, these findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux and further imply that EGCG may be a potential therapeutic reagent to prevent cardiovascular complications.