title: Endosulfan inducing apoptosis and necroptosis through activation RIPK signaling pathway in human umbilical vascular endothelial cells.
abstract: Endosulfan, an organochlorine pesticide, was found in human blood, and its possible cardiovascular toxicity has been suggested. However, the mechanism about endothelial cell injuries induced by endosulfan has remained unknown. In the present study, human umbilical vein endothelial cells (HUVECs) were chosen to explore the toxicity mechanism and were treated with 0, 1, 6, and 12 μg/mL-1endosulfan for 24 h, respectively. The results showed that exposure to endosulfan could inhibit the cell viability, increase the release of lactate dehydrogenase (LDH), damage the ultrastructure, and lead to apoptosis and necroptosis in HUVECs. Furthermore, endosulfan upregulated the expressions of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), mixed lineage kinase domain-like (MLKL), caspase 8, and caspase 3, which means the activation of RIPK1 pathways. In addition, endosulfan promoted the increases of ROS, IL-1α, and IL-33 levels while antioxidant N-acetyl-L-cysteine (NAC) effectively attenuated the cytotoxicity from endosulfan. Taken together, these results have demonstrated that endosulfan induces the apoptosis and necroptosis of HUVECs, where the RIPK pathway plays a pro-necroptotic role and NAC plays an anti-necroptotic role. Our results may contribute to understanding cellular mechanisms for endosulfan-induced cardiovascular toxicity.
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.|Department of Histology and Embryology, Bin Zhou Medical College, Yan Tai, 264003, China.
authors.forename: Lianshuang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Jialiu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China. manman-01@163.com.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. manman-01@163.com.
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China. xqzhou@ccmu.edu.cn.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. xqzhou@ccmu.edu.cn.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004726:Endosulfan / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D000067596:Interleukin-33 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C506536:IL33 protein, human; D007306:Insecticides; D000067596:Interleukin-33; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C109162:MAP3K13 protein, human; D004726:Endosulfan; D000111:Acetylcysteine
keywords: Apoptosis; Endosulfan; Human umbilical vascular endothelial cell; Necroptosis; RIPK