New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach
文献类型:期刊论文
作者 | Wang, Feidi1,2; Zhang, Haijun1; Geng, Ningbo1,2; Zhang, Baoqin1; Ren, Xiaoqian1,2; Chen, Jiping1 |
刊名 | ENVIRONMENTAL SCIENCE & TECHNOLOGY
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出版日期 | 2016-03-15 |
卷号 | 50期号:6页码:3145-3153 |
ISSN号 | 0013-936X |
DOI | 10.1021/acs.est.5b03678 |
文献子类 | Article |
英文摘要 | The toxic effects of hexabromocyclododecane (HBCD) are complex, and the underlying toxicological mechanisms are still not completely understood. In this study, a pseudotargeted metabolomic approach based on the UHPLC/Q-Trap MS system was developed to assess the HBCD-intervention-related metabolic alteration in HepG2 cells. In addition, some physiologic indicators and relevant enzyme activities were measured. HBCD exposure obviously impaired metabolic homeostasis and induced oxidative stress, even at an environmentally relevant dose (0.05 mg/L). Metabolic profiling and multivariate analysis indicated that the main metabolic pathways perturbed by HBCD included amino acid metabolism, protein biosynthesis, fatty acid metabolism, and phospholipid metabolism. HBCD suppressed the cell uptake of amino adds) mainly through inhibition of the activity of membrane transport protein Na+/K+-ATPase. HBCD down-regulated glycolysis and beta-oxidation of long-chain fatty acids, causing a large decrease of ATP production. As a result, the across-membrane transport of amino acids Was further inhibited. Meanwhile, HBCD induced a significant increase of total phospholipids, mainly through the remodeling of phospholipids from the increased free fatty acids. The obtained metabolomic results also provided some new evidence and clues regarding the toxicological mechanisms of HBCD that contribute to obesity, diabetes, nervous system damage, and developmental disorders. |
WOS关键词 | BROMINATED FLAME RETARDANTS ; HEPG2 CELLS ; TETRABROMOBISPHENOL-A ; GENE-EXPRESSION ; HEPATIC-ENZYMES ; HBCD ; GLUCOSE ; EXPOSURE ; PATHWAY ; RATS |
WOS研究方向 | Engineering ; Environmental Sciences & Ecology |
语种 | 英语 |
WOS记录号 | WOS:000372392100044 |
出版者 | AMER CHEMICAL SOC |
源URL | [http://cas-ir.dicp.ac.cn/handle/321008/171142] ![]() |
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; Chen, Jiping |
作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Feidi,Zhang, Haijun,Geng, Ningbo,et al. New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2016,50(6):3145-3153. |
APA | Wang, Feidi,Zhang, Haijun,Geng, Ningbo,Zhang, Baoqin,Ren, Xiaoqian,&Chen, Jiping.(2016).New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach.ENVIRONMENTAL SCIENCE & TECHNOLOGY,50(6),3145-3153. |
MLA | Wang, Feidi,et al."New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach".ENVIRONMENTAL SCIENCE & TECHNOLOGY 50.6(2016):3145-3153. |
入库方式: OAI收割
来源:大连化学物理研究所
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