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Title: | Akt mediates 17β-estradiol and/or estrogen receptor- inhibition of LPS-induced tumor necresis factor- expression and myocardial cell apoptosis by suppressing the JNK1/2-NFκB pathway |
Authors: | Liu, Chung-Jung Lo, Jeng-Fan Kuo, Chia-Hua Chu, Chun-Hsien Chen, Li-Ming Tsai, Fuu-Jen Tsai, Chang-Hai Tzang, Bor-Show Kuo, Wei-Wen Huang, Chih-Yang |
Contributors: | 中山醫學大學 醫學系生化科 |
Keywords: | myocardial cell apoptosis 17β-estradiol estrogen receptor- PI3K/Akt NFκB IκB lipopolysacchride JNK |
Date: | 2009-01-06 |
Issue Date: | 2012-08-10T07:42:07Z (UTC)
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ISSN: | 1582-1838 |
Abstract: | Evidence shows that women have lower tumour necrosis factor- (TNF-) levels and lower incidences of heart dysfunction and sepsis-related morbidity and mortality. To identify the cardioprotective effects and precise cellular/molecular mechanisms behind estrogen and estrogen receptors (ERs), we investigated the effects of 17β-estradiol (E2) and estrogen receptor (ER) on LPS-induced apoptosis by analyzing the activation of survival and death signalling pathways in doxycycline (Dox)-inducible Tet-On/ER H9c2 myocardial cells and ER-transfected primary cardiomyocytes overexpressing ER. We found that LPS challenge activated JNK1/2, and then induced IκB degradation, NFκB activation, TNF- up-regulation and subsequent myocardial apoptotic responses. In addition, treatments involving E2, membrane-impermeable BSA-E2 and/or Dox, which induces ER overexpression, significantly inhibited LPS-induced apoptosis by suppressing LPS-up-regulated JNK1/2 activity, IκB degradation, NFκB activation and pro-apoptotic proteins (e.g. TNF-, active caspases-8, t-Bid, Bax, released cytochrome c, active caspase-9, active caspase-3) in myocardial cells. However, the cardioprotective properties of E2, BSA-E2 and ER overexpression to inhibit LPS-induced apoptosis and promote cell survival were attenuated by applying LY294002 (PI3K inhibitor) and PI3K siRNA. These findings suggest that E2, BSA-E2 and ER expression exert their cardioprotective effects by inhibiting JNK1/2-mediated LPS-induced TNF- expression and cardiomyocyte apoptosis through activation of Akt. |
URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/4441 http://dx.doi.org/10.1111/j.1582-4934.2009.00669.x |
Relation: | Journal of Cellular and Molecular Medicine Volume 13, Issue 9b, pages 3655–3667, September 2009 |
Appears in Collections: | [醫學系] 期刊論文
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