Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage
Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage
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DOI：
10.1016/j.bbrc.2013.07.097
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发表时间：
2013-09-06
影响因子：
3.1
通讯作者：
Yan, Biao
中科院分区：
文献类型：
--
作者：
Li, Chao-Peng;Yao, Jin;Yan, Biao
自噬是一种通过溶酶体途径参与蛋白质和细胞器降解的细胞内分解代谢过程，与年龄相关性黄斑变性（AMD）的发病机制有关。UVB照射介导的黄斑视网膜色素上皮（RPE）细胞变性是AMD的重要标志，并伴随RPE自噬的改变。因此，RPE自噬的药理学操作可能为AMD提供另一种治疗靶点。本研究发现，绿茶中的一种多酚化合物表没食子儿茶素-3-没食子酸酯（EGCG）在UVB照射诱导的RPE细胞自噬中起调节作用。UVB照射导致LC3-II蛋白量呈剂量依赖性显著增加。EGCG可显著减少LC3-II和自噬体的形成。mTOR信号激活是egcg诱导LC3-II形成所必需的，事实证明，egcg诱导的LC3-II形成被雷帕霉素显著损害。此外，EGCG以自噬依赖的方式显著减轻UVB照射对RPE细胞的毒性作用。总之，我们的研究揭示了EGCG在RPE自噬中的新作用。EGCG可以作为一种潜在的治疗试剂，用于治疗与异常自噬相关的病理状况。Elsevier Inc.出版。
Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in-the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy. Published by Elsevier Inc.