Epigallocatechin-3-gallate attenuates microcystin-LR-induced apoptosis in human umbilical vein endothelial cells through activation of the NRF2/HO-1 pathway
Our previous study showed that the tea extract, epigallocatechin-3-gallate (EGCG), protects against microcystin-LR (MC-LR) -mediated apoptosis of human umbilical vein endothelial cells (HUVECs); however, the mechanism underlying MC-LR-induced HUVEC apoptosis remains incompletely understood. In this study, we investigated whether the nuclear factor erythroid-like 2 (NRF2)/heme oxygenase-1 (HO-1) pathway, which regulates antioxidant transcriptional regulation of oxidative stress and apoptosis, is involved in this process. Mitochondrial membrane potential (MMP) and caspase-3/-9 activities were evaluated in HUVECs by JC-1 staining and colorimetric activity assay, and a DCFH-DA fluorescent probe assay was used to quantitate reactive oxygen species (ROS) generation. The effects of MC-LR, EGCG, NF2, and HO-1 on HUVEC apoptosis were explored by western blotting and small interfering RNA (siRNA) analyses. MC-LR treatment downregulated HUVEC mitochondrial membrane potential, and decreased levels of cytochrome c release and activated caspase-3/-9, ROS generation, consequently inducing HUVEC apoptosis. EGCG treatment attenuated MC-LR-mediated HUVEC oxidative stress and mitochondria-related apoptosis. EGCG induced NRF2/HO-1 expression and activation in MC-LR treated HUVECs, while downregulation of NRF2/HO-1 by specific siRNAs revealed that NRF2/HO-1 signaling was involved in EGCG attenuation of MC-LR-induced HUVEC apoptosis. Our findings indicate that EGCG treatment protects against MC-LR-mediated HUVEC apoptosis via activation of NRF2/HO-1 signaling. (C) 2018 Elsevier Ltd. All rights reserved.
基金：
State Key Laboratory of Pollution
Control and Resource Reuse Foundation [NO. PCRRY16001],
National Natural Science Foundation of China [81401870] and
Major Science and Technology Program forWater Pollution Control
and Treatment [2017ZX07201003-02], China
第一作者机构：[1]Tongji Univ, Coll Environm Sci & Engn, State Key Lab Pollut Control & Resource Reuse, Shanghai, Peoples R China[3]Shanghai Inst Pollut Control & Ecol Safety, Shanghai, Peoples R China
通讯作者：
通讯机构：[2]Shanghai Jiao Tong Univ, TongRen Hosp, Div Cardiol, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China[*1]Division of Cardiology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, China
推荐引用方式(GB/T 7714)：
Shi Jun,Zhang Min,Zhang Libin,et al.Epigallocatechin-3-gallate attenuates microcystin-LR-induced apoptosis in human umbilical vein endothelial cells through activation of the NRF2/HO-1 pathway[J].ENVIRONMENTAL POLLUTION.2018,239:466-472.doi:10.1016/j.envpol.2018.04.038.
APA：
Shi, Jun,Zhang, Min,Zhang, Libin&Deng, Huipin.(2018).Epigallocatechin-3-gallate attenuates microcystin-LR-induced apoptosis in human umbilical vein endothelial cells through activation of the NRF2/HO-1 pathway.ENVIRONMENTAL POLLUTION,239,
MLA：
Shi, Jun,et al."Epigallocatechin-3-gallate attenuates microcystin-LR-induced apoptosis in human umbilical vein endothelial cells through activation of the NRF2/HO-1 pathway".ENVIRONMENTAL POLLUTION 239.(2018):466-472
环境科学与生态学