Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor a (PPAR alpha)
Gong, Yufeng2; Zhang, Haijun2; Geng, Ningbo2; Ren, Xiaoqian2,3; Giesy, John P.1,4,5; Luo, Yun2,3; Xing, Liguo6; Wu, Ping2; Yu, Zhengkun2; Chen, Jiping2
刊名ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
2019-10-15
卷号181页码:164-171
关键词SCCPs Mode of action PPAR alpha Luciferase assay Molecular docking Metabolomics
ISSN号0147-6513
DOI10.1016/j.ecoenv.2019.06.003
通讯作者Zhang, Haijun(hjzhang@dicp.ac.cn)
英文摘要Short-chain chlorinated paraffins (SCCPs) are frequently detected in environmental matrices and human tissues. It was hypothesized that SCCPs might interact with the peroxisome proliferator-activated receptor a (PPAR alpha). In the present study, an in vitro, dual-luciferase reporter gene assay and in silico molecular docking analysis were employed together to study the interactions between SCCPs congeners and PPAR alpha. Expressions of genes downstream in pathways activated by PPAR alpha in liver of rats exposed to 1, 10, or 100 mg/kg bm/d of C15-13-CPs (56.5% Cl) for 28 days were examined to confirm activation potencies of SCCPs toward PPAR alpha signaling. Effects of exposure to C10-13-CPs (56.5% Cl) on fatty acid metabolism in rat liver were also explored via a pseudo targeted metabolomics strategy. Our results showed that C10-13-CPs (56.5% Cl) caused a dose-dependent greater expression of luciferase activity of rat PPAR alpha. Molecular docking modeling revealed that SCCPs had a strong capacity to bind with PPAR alpha only through hydrophobic interactions and the binding affinity was dependent on the degree of chlorination in SCCPs congeners. In livers of male rats, exposure to 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) resulted in up-regulated expressions of 11 genes that are downstream in the PPAR alpha-activated pathway and regulate catabolism of fatty acid. Consistently, accelerated fatty acid oxidation was observed mainly characterized by lesser concentrations of Sigma fatty acids in livers of rats. Overall, these results demonstrated, for the first time, that SCCPs could activate rat PPAR alpha signaling and thereby disrupt metabolism of fatty acid in livers of male rats.
资助项目National Natural Science Foundation of China[21707140] ; National Natural Science Foundation of China[21337002] ; National Natural Science Foundation of China[21277141] ; Chinese National Basic Research Program[2015CB453100] ; China Postdoctoral Science Foundation[2016M601351] ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada
WOS关键词EXPRESSION ; EXPOSURE ; CARNITINE ; MECHANISM ; TOXICITY ; MOUSE ; BIOACCUMULATION ; ENHANCEMENT ; INDUCTION ; DISCOVERY
WOS研究方向Environmental Sciences & Ecology ; Toxicology
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000475411500019
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; Chinese National Basic Research Program ; Chinese National Basic Research Program ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Chinese National Basic Research Program ; Chinese National Basic Research Program ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Chinese National Basic Research Program ; Chinese National Basic Research Program ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Chinese National Basic Research Program ; Chinese National Basic Research Program ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada ; Canada Research Chairs Program of the Natural Science and Engineering Research Council of Canada
内容类型期刊论文
源URL[http://cas-ir.dicp.ac.cn/handle/321008/175365]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Zhang, Haijun
作者单位1.Baylor Univ, Dept Environm Sci, Waco, TX 76706 USA
2.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Saskatchewan, Dept Vet Biomed Sci, Saskatoon, SK S7N 5B4, Canada
5.Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK S7N 5B4, Canada
6.Shenyang Res Inst Chem Ind Ltd, Safety Evaluat Ctr, Shenyang 110021, Liaoning, Peoples R China
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Gong, Yufeng,Zhang, Haijun,Geng, Ningbo,et al. Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor a (PPAR alpha)[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2019,181:164-171.
APA Gong, Yufeng.,Zhang, Haijun.,Geng, Ningbo.,Ren, Xiaoqian.,Giesy, John P..,...&Chen, Jiping.(2019).Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor a (PPAR alpha).ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,181,164-171.
MLA Gong, Yufeng,et al."Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor a (PPAR alpha)".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 181(2019):164-171.
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