Paeoniflorin ameliorates ischemic injury in rat brain via inhibiting cytochrome c/caspase3/HDAC4 pathway
文献类型：期刊论文
| 作者 | Liu, Yi-fei1,2; Zhang, Lei1; Wu, Qi1,2; Feng, Lin-yin1,2
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2021-05-11 |
| 页码 | 12 |
| 关键词 | ischemic brain injury paeoniflorin MCAO HDAC4 cytochrome c apoptosis |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-021-00671-y |
| 通讯作者 | Feng, Lin-yin(lyfeng@simm.ac.cn) |
| 英文摘要 | Paeoniflorin (PF), a bioactive monoterpene glucoside, has shown a variety of pharmacological effects such as anti-inflammation and autophagy modulation etc. In this study, we investigated whether and how PF exerted a protective effect against ischemic brain injury in vivo and in vitro. Primary rat cortical neurons underwent oxygen/glucose deprivation/reperfusion (OGD/R) for 90 min. We showed that after OGD/R, a short fragment of histone deacetylase 4 (HDAC4) produced by caspase3-mediated degradation was markedly accumulated in the nucleus and the activity of caspase3 was increased. Treatment with PF (100 nM, 1 mu M) significantly improved the viability of cortical neurons after OGD/R. Furthermore, PF treatment could maintain HDAC4 intrinsic subcellular localization and reduce the caspase3 activity without changing the HDAC4 at the transcriptional level. PF treatment significantly reduced OGD/R-caused inhibition of transcriptional factor MEF2 expression and increased the expression of downstream proteins such as GDNF, BDNF, and Bcl-xl, thus exerting a great anti-apoptosis effect as revealed by TUNEL staining. The beneficial effects of PF were almost canceled in HDAC4 (D289E)-transfected PC12 cells after OGD/R. In addition, PF treatment reduced the caspase9 activity, rescued the release of cytochrome c from mitochondria, and maintained the integrity of mitochondria membrane. We conducted in vivo experiments in 90-min-middle cerebral artery occlusion (MCAO) rat model. The rats were administered PF (20, 40 mg/kg, ip, 3 times at the reperfusion, 24 h and 48 h after the surgery). We showed that PF administration dose-dependently reduced infarction area, improved neurological symptoms, and maintained HDAC4 localization in rats after MCAO. These results demonstrate that PF is effective in protecting against ischemic brain injury and inhibit apoptosis through inhibiting the cytochrome c/caspase3/HDAC4 pathway. |
| WOS关键词 | HISTONE DEACETYLASES ; NUCLEAR EXPORT ; STROKE ; MECHANISMS ; DAMAGE ; HEART |
| 资助项目 | National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-003-013] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA12040304] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA12040216] ; Shanghai Committee of Science and Technology, China[18DZ2290200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000649246300001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296624]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Feng, Lin-yin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Neuropharmacol, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yi-fei,Zhang, Lei,Wu, Qi,et al. Paeoniflorin ameliorates ischemic injury in rat brain via inhibiting cytochrome c/caspase3/HDAC4 pathway[J]. ACTA PHARMACOLOGICA SINICA,2021:12. |
| APA | Liu, Yi-fei,Zhang, Lei,Wu, Qi,&Feng, Lin-yin.(2021).Paeoniflorin ameliorates ischemic injury in rat brain via inhibiting cytochrome c/caspase3/HDAC4 pathway.ACTA PHARMACOLOGICA SINICA,12. |
| MLA | Liu, Yi-fei,et al."Paeoniflorin ameliorates ischemic injury in rat brain via inhibiting cytochrome c/caspase3/HDAC4 pathway".ACTA PHARMACOLOGICA SINICA (2021):12. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。