Cadmium exposure promotes ferroptosis by upregulating Heat Shock Protein 70 in vascular endothelial damage of zebrafish

作者全名："Zhang, Tian; Yan, Wenhua; Liu, Cong; Duan, Weixia; Duan, Yu; Li, Yuanyuan; Yu, Qin; Sun, Yapei; Tian, Jiacheng; Zhou, Jie; Xia, Zhiqin; Wang, Guixue; Xu, Shangcheng"

作者地址："[Zhang, Tian; Wang, Guixue; Xu, Shangcheng] Chongqing Univ, Bioengn Coll, Key Lab Biorheol Sci & Technol, State & Local Joint Engn Lab Vasc Implants, 174 Shazhengjie, Chongqing 400044, Peoples R China; [Zhang, Tian; Liu, Cong; Duan, Weixia; Duan, Yu; Li, Yuanyuan; Yu, Qin; Sun, Yapei; Tian, Jiacheng; Zhou, Jie; Xia, Zhiqin; Xu, Shangcheng] Chongqing Key Lab Prevent & Treatment Ctr Occupat, Chongqing 400060, Peoples R China; [Yan, Wenhua] Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Wang, GX; Xu, SC (通讯作者)，Chongqing Univ, Bioengn Coll, Key Lab Biorheol Sci & Technol, State & Local Joint Engn Lab Vasc Implants, 174 Shazhengjie, Chongqing 400044, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001045047400001

JCR分区：Q1

影响因子：6.2

年份：2023

卷号：263

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Cadmium; Ferroptosis; Heat Shock Protein 70; Vascular endothelial cells

摘要："Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process."

基金机构："National Natural Science Foundation of China [82073523, 31971242]; Chongqing Science Foundation for Distinguished Young Scholars grant [cstc2020jcyj-jqx0027]; Chongqing Youth Talent Project [CQYC201905029]"

基金资助正文："This article was supported by National Natural Science Foundation of China grant (No. 82073523, to S. C. X.; No. 31971242, to G. X. W.) , Chongqing Science Foundation for Distinguished Young Scholars grant (No. cstc2020jcyj-jqx0027, to S. C. X.) , Chongqing Youth Talent Project grant (No. CQYC201905029, to S. C. X.) ."