2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway
文献类型：期刊论文
| 作者 | Yu, Yu2,3; Liu, Qian3; Guo, Shumin3,4; Kong, Deping3,4; Yu, Ying3,4; Liu, Qian4; Zhang, Qianqian4; Tang, Juan4; Liu, Guizhu4; Li, Juanjuan4 |
| 刊名 | JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
 |
| 出版日期 | 2017 |
| 卷号 | 21期号:12页码:3540-3551 |
| ISSN号 | 1582-4934 |
| 关键词 | dioxin endothelial cell apoptosis EP3 p38 MAPK Bcl-2 |
| DOI | 10.1111/jcmm.13265 |
| 文献子类 | Article |
| 英文摘要 | Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to different doses of TCDD, and cell apoptosis was examined. We found that TCDD treatment increased caspase 3 activity and apoptosis in HUVECs in a dose-dependent manner,at doses from 10 to 40 nM. TCDD increased cyclooxygenase enzymes (COX)-2 expression and its downstream prostaglandin (PG) production (mainly PGE(2) and 6-keto-PGF(1 alpha)) in HUVECs. Interestingly, inhibition of COX-2, but not COX-1, markedly attenuated TCDD-triggered apoptosis in HUVECs. Pharmacological inhibition or gene silencing of the PGE(2) receptor subtype 3 (EP3) suppressed the augmented apoptosis in TCDD-treated HUVECs. Activation of the EP3 receptor enhanced p38 MAPK phosphorylation and decreased Bcl-2 expression following TCDD treatment. Both p38 MAPK suppression and Bcl-2 overexpression attenuated the apoptosis in TCDD-treated HUVECs. TCDD increased EP3-dependent Rho activity and subsequently promoted p38MAPK/Bcl-2 pathway-mediated apoptosis in HUVECs. In addition, TCDD promoted apoptosis in vascular endothelium and delayed re-endothelialization after femoral artery injury in wild-type (WT) mice, but not in EP3(-/-) mice. In summary, TCDD promotes endothelial apoptosis through the COX-2/PGE(2)/EP3/p38MAPK/Bcl-2 pathway. Given the cardiovascular hazard of a COX-2 inhibitor, our findings indicate that the EP3 receptor and its downstream pathways may be potential targets for prevention of TCDD-associated cardiovascular diseases. |
| 学科主题 | Cell Biology ; Research & Experimental Medicine |
| WOS关键词 | TCDD-INDUCED APOPTOSIS ; E-DEFICIENT MICE ; SIGNALING PATHWAY ; INCREASES APOPTOSIS ; GENE-EXPRESSION ; ATHEROSCLEROSIS ; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ; RECEPTOR ; DYSFUNCTION ; PROLIFERATION |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000418574500036 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/514]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Agr Sci, Inst Qual Stand & Testing Technol Agroprod, Beijing, Peoples R China, 2.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pediat Cardiol, Shanghai, Peoples R China; 3.Tianjin Med Univ, Dept Pharmacol, Tianjin, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yu, Yu,Liu, Qian,Guo, Shumin,et al. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2017,21(12):3540-3551. |
| APA | Yu, Yu.,Liu, Qian.,Guo, Shumin.,Kong, Deping.,Yu, Ying.,...&,.(2017).2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,21(12),3540-3551. |
| MLA | Yu, Yu,et al."2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 21.12(2017):3540-3551. |
入库方式： OAI收割
来源：上海营养与健康研究所
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