Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

被引:53
作者
Li, Sainan [1 ]
Xia, Yujing [1 ]
Chen, Kan [1 ]
Li, Jingjing [1 ]
Liu, Tong [1 ]
Wang, Fan [1 ]
Lu, Jie [1 ]
Zhou, Yingqun [1 ]
Guo, Chuanyong [1 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai 200072, Peoples R China
基金
中国国家自然科学基金;
关键词
concanavalin A; hepatitis; EGCG; autophagy; apoptosis; BNIP3; STAT3; JAKs; IL-6; ORAL POLYPHENON E; RAI STAGE 0; CELL-DEATH; BH3-ONLY PROTEINS; URSODEOXYCHOLIC ACID; COMBINATION THERAPY; LIVER-DISEASE; MITOCHONDRIAL; EGCG; GALLATE;
D O I
10.2147/DDDT.S99420
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: Epigallocatechin-3-gallate (EGCG) is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA)-induced hepatitis in mice and explored the possible mechanisms involved in these effects. Methods: Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg) was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration. Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-alpha, IL-6, IFN-gamma, and IL-1 beta. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway. Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy.
引用
收藏
页码:631 / 647
页数:17
相关论文
共 83 条
[1]   Ways of dying: multiple pathways to apoptosis [J].
Adams, JM .
GENES & DEVELOPMENT, 2003, 17 (20) :2481-2495
[2]   Mechanisms of cell death in acute liver failure [J].
Bantel, Heike ;
Schulze-Osthoff, Klaus .
FRONTIERS IN PHYSIOLOGY, 2012, 3
[3]   Decoding cell death signals in liver inflammation [J].
Brenner, Catherine ;
Galluzzi, Lorenzo ;
Kepp, Oliver ;
Kroemer, Guido .
JOURNAL OF HEPATOLOGY, 2013, 59 (03) :583-594
[4]   The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death [J].
Burton, T. R. ;
Gibson, S. B. .
CELL DEATH AND DIFFERENTIATION, 2009, 16 (04) :515-523
[5]   Epigallocatechin-3-gallate ameliorates both obesity and autoinflammatory arthritis aggravated by obesity by altering the balance among CD4+ T-cell subsets [J].
Byun, Jae-Kyeong ;
Yoon, Bo-Young ;
Jhun, Joo-Yeon ;
Oh, Hye-Joa ;
Kim, Eun-Kyoung ;
Min, Jun-Ki ;
Cho, Mi-La .
IMMUNOLOGY LETTERS, 2014, 157 (1-2) :51-59
[6]   15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity [J].
Chen, Kan ;
Li, Jingjing ;
Wang, Junshan ;
Xia, Yujing ;
Dai, Weiqi ;
Wang, Fan ;
Shen, Miao ;
Cheng, Ping ;
Zhang, Yan ;
Wang, Chengfen ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Zheng, Yuanyuan ;
Lu, Jie ;
Fan, Zhuoyi ;
Zhou, Yingqun ;
Guo, Chuanyong .
PPAR RESEARCH, 2014, 2014
[7]   Autophagy Inhibition Contributes to the Synergistic Interaction between EGCG and Doxorubicin to Kill the Hepatoma Hep3B Cells [J].
Chen, Li ;
Ye, Hui-Lan ;
Zhang, Guo ;
Yao, Wen-Min ;
Chen, Xing-Zhou ;
Zhang, Fa-Can ;
Liang, Gang .
PLOS ONE, 2014, 9 (01)
[8]   Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis [J].
Cheng, Ping ;
Chen, Kan ;
Xia, Yujing ;
Dai, Weiqi ;
Wang, Fan ;
Shen, Miao ;
Wang, Chengfen ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Li, Jingjing ;
Zheng, Yuanyuan ;
Wang, Junshan ;
Zhang, Yan ;
Lu, Jie ;
Zhou, Yingqun ;
Guo, Chuanyong .
DRUG DESIGN DEVELOPMENT AND THERAPY, 2014, 8 :1277-1286
[9]   Hydrogen Sulfide Ameliorates Ischemia/Reperfusion-Induced Hepatitis by Inhibiting Apoptosis and Autophagy Pathways [J].
Cheng, Ping ;
Wang, Fan ;
Chen, Kan ;
Shen, Miao ;
Dai, Weiqi ;
Xu, Ling ;
Zhang, Yan ;
Wang, Chengfen ;
Li, Jingjing ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Zheng, Yuanyuan ;
Lu, Jie ;
Zhou, Yingqun ;
Guo, Chuanyong .
MEDIATORS OF INFLAMMATION, 2014, 2014
[10]   BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions [J].
Chinnadurai, G. ;
Vijayalingam, S. ;
Gibson, S. B. .
ONCOGENE, 2008, 27 (Suppl 1) :S114-S127