Endosulfan induces autophagy and endothelial dysfunction via the AMPK/mTOR signaling pathway triggered by oxidative stress.
Cardiovascular diseases is related to environmental pollution. Endosulfan is an organochlorine pesticide and its toxicity has been reported. However, the relationship between oxidative stress and autophagy induced by endosulfan and its underlying mechanism remain confusing. In this study, human umbilical vein endothelial cells (HUVECs) were chosen to explore the toxicity mechanism and were treated with 0, 1, 6, 12 μg/mL-1endosulfan for 24 h, respectively. The present results showed that autophagy could be induced by endosulfan, which was verified by the monodansylcadaverine staining, autophagic ultrastructural observation, and LC3-I/LC3-II conversion. In addition, the levels of adenosine triphosphate (ATP), the mitochondria membrane potential (MMP) were significantly decreased in a dose-dependent way. The expression of proinflammatory cytokines (tumor necrosis factor α, interleukin-1β, and interleukin-6) were significantly elevated, and the index of endothelial function such as monocyte chemotactic protein 1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) increased. Moreover, endosulfan had an activation effect on the 5'AMP-activated protein kinase (AMPK)/rapamycin (mTOR) signaling pathway. Our findings demonstrated that endosulfan could induce oxidative stress and mitochondria injury, activate autophagy, induce inflammatory response, and eventually lead to endothelial dysfunction via the AMPK/mTOR pathway. This indicates that exposure to endosulfan is a potential risk factor for cardiovascular diseases.
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.
Lianshuang
L
Zhang
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.
Jialiu
J
Wei
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.
Lihua
L
Ren
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.
Jin
J
Zhang
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.
Ji
J
Wang
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.
Li
L
Jing
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.
Man
M
Yang
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.
Yang
Y
Yu
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.
Zhiwei
Z
Sun
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. Electronic address: xqzhou@ccmu.edu.cn.
Xianqing
X
Zhou
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D004726:Endosulfan / Q000378:metabolism* / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D055372:AMP-Activated Protein Kinases; D004726:Endosulfan