Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: Caspases and Endonuclease G (Endo G) pathway
文献类型：期刊论文
| 作者 | Cai, Y; Qi, XM ; Gong, LK; Liu, LL; Chen, FP; Xiao, Y; Wu, XF; Li, XH; Ren, J
|
| 刊名 | TOXICOLOGY
 |
| 出版日期 | 2006-01-20 |
| 卷号 | 218期号:1页码:1-12 |
| 关键词 | tetrandrine rat primary hepatocytes mitochondria caspase 3 Endo G |
| ISSN号 | 0300-483X |
| DOI | 10.1016/j.tox.2005.08.024 |
| 文献子类 | Article |
| 英文摘要 | Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra (S Moore), possesses a remarkable pharmacological profile. However, the mechanisms of tetrandrine hepatotoxicity remain to be elucidated. In this study, we first proved apoptosis and mitochondrial dysfunction induced by tetrandrine in Sprague-Dawley rat liver in vivo. By further assuming apoptosis as an important mechanism in tetrandrine-induced hepatotoxicity, we focused on mitochondria-initiated apoptosis in primary hepatocytes isolated from Sprague-Dawley male rats. Tetrandrine treatment led to significant release of cytochrome c and downregulation of Bcl-X-L accompanied by caspase 3 activation, and ultimately, DNA fragmentation. Caspase 3 activation was markedly inhibited by cyclosporin A (CsA) and Ac-DEVD-CHO. Furthermore, Endo G, a caspase-independent apoptotic protein, was detected for its expression and DNase activity. CsA blocked the release both of Endo G and cytochrome c significantly. Additionally, the generation of reactive oxygen species (ROS) increased in a time-dependent manner corresponding with a fall in intracellular GSH content after 10 mu M tetrandrine treatment in 4h. Tetrandrine also induced mitochondrial dysfunction indicated by transition of mitochondrial transmembrane potential and decrease of intracellular ATP level. The findings indicated that the caspase-dependent mitochondrial apoptosis pathway was primarily involved in tetrandrine-induced apoptosis in rat primary hepatocytes. In addition, a caspase-independent pathway indicated by Endo G also contributed to apoptosis caused by tetrandrine. Meanwhile, ROS was proved an important inducer in this apoptosis process. (c) 2005 Elsevier Ireland Ltd. All rights reserved. |
| WOS关键词 | CELL-DEATH ; OXIDATIVE STRESS ; CYTOCHROME-C ; CYTOTOXICITY ; RELEASE ; GENOTOXICITY ; DYSFUNCTION ; INHIBITION ; GENERATION ; INDUCTION |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000234844300001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273688]  |
| 专题 | 药物安全性评价中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ren, J |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Y,Qi, XM,Gong, LK,et al. Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: Caspases and Endonuclease G (Endo G) pathway[J]. TOXICOLOGY,2006,218(1):1-12. |
| APA | Cai, Y.,Qi, XM.,Gong, LK.,Liu, LL.,Chen, FP.,...&Ren, J.(2006).Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: Caspases and Endonuclease G (Endo G) pathway.TOXICOLOGY,218(1),1-12. |
| MLA | Cai, Y,et al."Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: Caspases and Endonuclease G (Endo G) pathway".TOXICOLOGY 218.1(2006):1-12. |
入库方式： OAI收割
来源：上海药物研究所
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