A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells.
A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells.
复制标题
HepG2细胞中EGCG介导的AFP自噬调节的新分子机制
DOI：
10.1038/cddis.2017.563
复制
发表时间：
2017-11-02
影响因子：
9
通讯作者：
Zhou R
中科院分区：
文献类型：
--
作者：
Zhao L;Liu S;Xu J;Li W;Duan G;Wang H;Yang H;Yang Z;Zhou R
Epigallocatechingallate（EGCG）是绿茶的主要生物活性成分，与包括癌症在内的多种疾病有关的健康益处。在这项研究中，癌细胞的预后不良，EGCG可以有效地减少AFP的分泌，并在人类HCC HEPG2细胞中诱导AFP聚集。 EGCG刺激的自噬诱导了HEPG2细胞中的AFP聚集体的降解，我们通过使用大型的全元素分子动力学模拟了EGCG刺激的自噬的基本分子机制使用LC3-I蛋白，很容易将后者的关键GLY-120位点暴露于其他重要的结合伙伴，例如1,2-脱酰酰基-SN-甘油-3-磷酸乙醇胺，并促进LC3-II的合成，这是一种特征性的自噬体标记，我们的结果表明EGCG在调节AFP分泌和提供分子的自噬活性时至关重要。潜在预防和治疗HCC的基础。
Epigallocatechingallate (EGCG) is a major bioactive component of green tea and is associated with health benefits against multiple diseases including cancer. As an indicator of hepatocellular carcinoma (HCC), high levels of α-fetal protein (AFP) are related to malignant differentiation and poor prognosis of cancer cells. In this study, EGCG can effectively reduce AFP secretion and simultaneously induce AFP aggregation in human HCC HepG2 cells. EGCG-stimulated autophagy induces the degradation of AFP aggregates in HepG2 cells. Furthermore, we thoroughly studied the underlying molecular mechanisms behind EGCG-stimulated autophagy by using large-scale all-atom molecular dynamics simulations, which revealed a novel molecular mechanism. EGCG directly interacts with LC3-I protein, readily exposing the pivotal Gly-120 site of the latter to other important binding partners such as 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and promoting the synthesis of LC3-II, a characteristic autophagosomal marker. Our results suggest that EGCG is critical in regulating AFP secretion and in modulating autophagic activities of HepG2 cells, providing a molecular basis for potentially preventing and treating HCC.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
38.3
作者：
通讯作者：
--
无去污剂条件下合成自噬体标记蛋白 LC3-II。
影响因子：
16.6
作者：
Huang, Yi-Chao;Li, Yi-Ming;Liu, Lei
通讯作者：
Liu, Lei
影响因子：
4.4
作者：
Bussi, Giovanni;Donadio, Davide;Parrinello, Michele
通讯作者：
Parrinello, Michele
影响因子：
6.4
作者：
Li, Mengsen;Li, Hui;Li, Gang
通讯作者：
Li, Gang