Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways

Wei, Jialiu, Zhang, Lianshuang, Ren, Lihua, Zhang, Jin, Liu, Jianhui, Duan, Junchao, Yu, Yang, Li, Yanbo , Peng, Cheng, Zhou, Xianqing and Sun, Zhiwei (2017) Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways. Science of the Total Environment, 589 97-106. doi:10.1016/j.scitotenv.2017.02.154


Author Wei, Jialiu
Zhang, Lianshuang
Ren, Lihua
Zhang, Jin
Liu, Jianhui
Duan, Junchao
Yu, Yang
Li, Yanbo
Peng, Cheng
Zhou, Xianqing
Sun, Zhiwei
Title Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways
Journal name Science of the Total Environment   Check publisher's open access policy
ISSN 1879-1026
0048-9697
Publication date 2017-07-01
Sub-type Article (original research)
DOI 10.1016/j.scitotenv.2017.02.154
Open Access Status Not yet assessed
Volume 589
Start page 97
End page 106
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2018
Language eng
Formatted abstract
Our previous study showed that endosulfan increases the risk of cardiovascular disease. To identify toxic mechanism of endosulfan, we conducted an animal study for which 32 male Wistar rats were randomly and equally divided into four groups: Control group (corn oil only) and three treatment groups (1, 5 and 10 mg kg−1·d−1). The results showed that exposure to endosulfan resulted in injury of cardiac tissue with impaired mitochondria integrity and elevated 8-OHdG expression in myocardial cells. Moreover, endosulfan increased the expressions of Fas, FasL, Caspase-8, Cleaved Caspase-8, Caspase-3 and Cleaved Caspase-3 in cardiac tissue. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of endosulfan (1, 6 and 12 μg mL−1) for 24 h. An inhibitor for Ataxia Telangiectasia Mutated Protein (ATM) (Ku-55933, 10 μM) was added in 12 μg mL−1 group for 2 h before exposure to endosulfan. Results showed that endosulfan induced DNA damage and activated DNA damage response signaling pathway (ATM/Chk2 and ATR/Chk1) and consequent cell cycle checkpoint. Furthermore, endosulfan promoted the cell apoptosis through death receptor pathway resulting from oxidative stress. The results provide a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan.
Keyword DNA damage
DNA damage response
Endosulfan
HUVECs
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
National Research Centre for Environmental Toxicology Publications
 
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