PMID- 27814983
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20181202
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 220
IP  - Pt B
DP  - 2017 Jan
TI  - Endosulfan induces autophagy and endothelial dysfunction via the AMPK/mTOR 
      signaling pathway triggered by oxidative stress.
PG  - 843-852
LID - S0269-7491(16)30825-9 [pii]
LID - 10.1016/j.envpol.2016.10.067 [doi]
AB  - 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 mug/mL(-1) endosulfan 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 alpha, interleukin-1beta, 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.
CI  - Copyright A(c) 2016 Elsevier Ltd. All rights reserved.
FAU - Zhang, Lianshuang
AU  - Zhang L
AD  - 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.
FAU - Wei, Jialiu
AU  - Wei J
AD  - 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.
FAU - Ren, Lihua
AU  - Ren L
AD  - 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.
FAU - Zhang, Jin
AU  - Zhang J
AD  - 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.
FAU - Wang, Ji
AU  - Wang J
AD  - 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.
FAU - Jing, Li
AU  - Jing L
AD  - 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.
FAU - Yang, Man
AU  - Yang M
AD  - 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.
FAU - Yu, Yang
AU  - Yu Y
AD  - 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.
FAU - Sun, Zhiwei
AU  - Sun Z
AD  - 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.
FAU - Zhou, Xianqing
AU  - Zhou X
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20161101
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - OKA6A6ZD4K (Endosulfan)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Autophagy/*drug effects
MH  - Endosulfan/*metabolism/*toxicity
MH  - Human Umbilical Vein Endothelial Cells/*drug effects
MH  - Humans
MH  - Oxidative Stress/*drug effects
MH  - Signal Transduction/*drug effects
EDAT- 2016/11/07 06:00
MHDA- 2017/03/10 06:00
CRDT- 2016/11/06 06:00
PHST- 2016/08/16 00:00 [received]
PHST- 2016/10/19 00:00 [revised]
PHST- 2016/10/23 00:00 [accepted]
PHST- 2016/11/07 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
PHST- 2016/11/06 06:00 [entrez]
AID - S0269-7491(16)30825-9 [pii]
AID - 10.1016/j.envpol.2016.10.067 [doi]
PST - ppublish
SO  - Environ Pollut. 2017 Jan;220(Pt B):843-852. doi: 10.1016/j.envpol.2016.10.067. 
      Epub 2016 Nov 1.