Endosulfan inducing apoptosis and necroptosis through activation RIPK signaling pathway in human umbilical vascular endothelial cells

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• 作者：Lianshuang Zhang ; Jialiu Wei ; Lihua Ren…
• 关键词：Endosulfan ; RIPK ; Apoptosis ; Necroptosis ; Human umbilical vascular endothelial cell
• 刊名：Environmental Science and Pollution Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：24
• 期：1
• 页码：215-225
• 全文大小：
• 刊物类别：Earth and Environmental Science
• 刊物主题：Environment, general; Environmental Chemistry; Ecotoxicology; Environmental Health; Atmospheric Protection/Air Quality Control/Air Pollution; Waste Water Technology / Water Pollution Control / Water M
• 出版者：Springer Berlin Heidelberg
• ISSN：1614-7499
• 卷排序：24

文摘

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−1 endosulfan 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.