Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway
文献类型：期刊论文
| 作者 | Li, Dong-Ping1; Chen, Ying-Ling1; Jiang, Hong-Yue1; Chen, Yun1; Zeng, Xiao-Qing1; Xu, Li-Li1; Ye, Yang2 ; Ke, Chang-Qiang2; Lin, Ge3; Wang, Ji-Yao1,4
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| 刊名 | DRUG DESIGN DEVELOPMENT AND THERAPY
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| 出版日期 | 2019-05-15 |
| 卷号 | 13页码:2081-2096 |
| 关键词 | Gynura segetum apoptosis mitochondrial ROS SIRT3 phosphocreatine |
| ISSN号 | 1177-8881 |
| DOI | 10.2147/DDDT.S203564 |
| 文献子类 | Article |
| 英文摘要 | Purpose: To investigate the mitochondria-related mechanism of Gynura segetum (GS)-induced apoptosis and the protective effect of phosphocreatine (PCr), a mitochondrial respiration regulator. Methods: First, the mechanism was explored in human hepatocyte cell line. The mitochondrial oxidative stress was determined by fluorescence assay. The level of sirtuin 3 (SIRT3), acetylated superoxide dismutase 2 (Ac-SOD2), SOD2, and apoptosis were detected byWestern blotting. Mito-TEMPO and cell lines of viral vector-mediated overexpression of SIRT3 and SIRT3(H248Y) were used to further verify the mechanism of GS-induced apoptosis. GS-induced liver injury mice models were built by GS through intragastric administration and interfered by PCr through intraperitoneal injection. A total of 30 C57BL/6J mice were assigned to 5 groups and treated with either saline, PCr (100 mg/kg), GS (30 g/kg), or PCr (50 or 100 mg/kg)+ GS (30 g/kg). Liver hematoxylin and eosin (HE) staining, immunohistochemical analysis, and blood biochemical evaluation were performed. Results: GS induced hepatocyte apoptosis and elevated levels of mitochondrial ROS in L-02 cells. The expression of SIRT3 was decreased. Downregulation of SIRT3 was associated with increased levels of Ac-SOD2, which is the inactivated enzymatic form of SOD2. Conversely, when overexpressing SIRT3 in GS-treated cells, SOD2 activity was restored, and mitochondrial ROS levels and hepatocyte apoptosis declined. Upon administration of PCr to GS-treated cells, they exhibited a significant upregulation of SIRT3 and were protected against apoptosis. In animal experiments, serum ALT level and mitochondrial ROS of the mice treated with GS and 50 mg/kg PCr were significantly attenuated compared with only GS treated. The changes in SIRT3 expression were also consistent with the in vitro results. In addition, immunohistochemical analysis of the mouse liver showed that Ac-SOD2 was decreased in the PCr and GS co-treated group compared with GS treated group. Conclusion: GS caused liver injury by dysregulating mitochondrial ROS generation via a SIRT3-SOD2 pathway. PCr is a potential agent to treat GS-induced liver injury by mitochondrial protection. |
| WOS关键词 | HEPATOTOXIC PYRROLIZIDINE ALKALOIDS ; MANGANESE SUPEROXIDE-DISMUTASE ; OXIDATIVE STRESS ; PROTECTS ; CELLS ; EXPRESSION ; INJURY ; ACTIVATION ; INDUCTION ; SOD2 |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000473360600001 |
| 出版者 | DOVE MEDICAL PRESS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309438]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Hong |
| 作者单位 | 1.Fudan Univ, Zhongshan Hosp, Dept Gastroenterol & Hepatol, 180 Fenglin Rd, Shanghai 200032, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Nat Prod, Chem Dept, Pudong, Peoples R China; 3.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China; 4.Fudan Univ, Evidance Based Med Ctr, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Dong-Ping,Chen, Ying-Ling,Jiang, Hong-Yue,et al. Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2019,13:2081-2096. |
| APA | Li, Dong-Ping.,Chen, Ying-Ling.,Jiang, Hong-Yue.,Chen, Yun.,Zeng, Xiao-Qing.,...&Gao, Hong.(2019).Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway.DRUG DESIGN DEVELOPMENT AND THERAPY,13,2081-2096. |
| MLA | Li, Dong-Ping,et al."Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway".DRUG DESIGN DEVELOPMENT AND THERAPY 13(2019):2081-2096. |
入库方式： OAI收割
来源：上海药物研究所
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