The PGC-1 alpha Activator ZLN005 Ameliorates Ischemia-Induced Neuronal Injury In Vitro and In Vivo
文献类型：期刊论文
| 作者 | Xu, Yazhou3; Kabba, John Alimamy3; Ruan, Wenchen3; Wang, Yunjie3; Zhao, Shunyi3; Song, Xiaoyue2; Zhang, Luyong3; Li, Jia1 ; Pang, Tao3
|
| 刊名 | CELLULAR AND MOLECULAR NEUROBIOLOGY
 |
| 出版日期 | 2018-05 |
| 卷号 | 38期号:4页码:929-939 |
| 关键词 | Ischemic stroke PGC-1 alpha HO-1 Neuroprotection |
| ISSN号 | 0272-4340 |
| DOI | 10.1007/s10571-017-0567-0 |
| 文献子类 | Article |
| 英文摘要 | Oxidative stress is a great challenge to neurons following cerebral ischemia. PGC-1 alpha has been shown to act as a potent modulator of oxidative metabolism. In this study, the effects of ZLN005, a small molecule that activate PGC-1 alpha, against oxygen-glucose deprivation (OGD)- or ischemia-induced neuronal injury in vitro and in vivo were investigated. Transient middle cerebral artery occlusion (tMCAO) was performed in rats and ZLN005 was administered intravenously at 2 h, 4 h, or 6 h after ischemia onset. Infarct volume and neurological deficit score were detected to evaluate the neuroprotective effects of ZLN005. Well-differentiated PC12 cells, which were subjected to OGD for 2 h followed by reoxygenation for 22 h, were used as an in vitro ischemic model. Changes in expression of PGC-1 alpha, its related genes, and antioxidant genes were determined by real-time quantitative PCR. The results showed that ZLN005 reduced cerebral infarct volume and improved the neurological deficit in rat with tMCAO, and significantly protected OGD-induced neuronal injury in PC12 cells. Furthermore, ZLN005 enhanced expression of PGC-1 alpha in PC12 cells and in the ipsilateral hemisphere of rats with tMCAO. Additionally, ZLN005 increased antioxidant genes, including SOD1 and HO-1, and significantly prevented the ischemia-induced decrease in SOD activity. Taking together, the PGC-1 alpha activator ZLN005 exhibits neuroprotective effects under ischemic conditions and molecular mechanisms possibly involve activation of PGC-1 alpha signaling pathway and cellular antioxidant systems. |
| WOS关键词 | CEREBRAL-ARTERY OCCLUSION ; INDUCED OXIDATIVE STRESS ; NRF2 SIGNALING PATHWAY ; MITOCHONDRIAL BIOGENESIS ; REPERFUSION INJURY ; INDUCED APOPTOSIS ; PC12 CELLS ; MICROGLIA ACTIVATION ; HO-1 EXPRESSION ; BRAIN-INJURY |
| 资助项目 | National Natural Science Foundation of China[21402241] ; Natural Science Foundation of Jiangsu Province[BK20160032] ; Six Talent Peaks Project of Jiangsu Province[00000000] ; Program for Jiangsu Province "Shuang Chuang" Team[00000000] |
| WOS研究方向 | Cell Biology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000429108800015 |
| 出版者 | SPRINGER/PLENUM PUBLISHERS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279789]  |
| 专题 | 国家新药筛选中心 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 药物安全性评价中心 |
| 通讯作者 | Pang, Tao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Liverpool, Sch Biol Sci, Brownlow Hill, Liverpool L69 3BX, Merseyside, England; 3.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, State Key Lab Nat Med, Jiangsu Key Lab Drug Discovery Metab Dis, 24 Tong Jia Xiang St, Nanjing 210009, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xu, Yazhou,Kabba, John Alimamy,Ruan, Wenchen,et al. The PGC-1 alpha Activator ZLN005 Ameliorates Ischemia-Induced Neuronal Injury In Vitro and In Vivo[J]. CELLULAR AND MOLECULAR NEUROBIOLOGY,2018,38(4):929-939. |
| APA | Xu, Yazhou.,Kabba, John Alimamy.,Ruan, Wenchen.,Wang, Yunjie.,Zhao, Shunyi.,...&Pang, Tao.(2018).The PGC-1 alpha Activator ZLN005 Ameliorates Ischemia-Induced Neuronal Injury In Vitro and In Vivo.CELLULAR AND MOLECULAR NEUROBIOLOGY,38(4),929-939. |
| MLA | Xu, Yazhou,et al."The PGC-1 alpha Activator ZLN005 Ameliorates Ischemia-Induced Neuronal Injury In Vitro and In Vivo".CELLULAR AND MOLECULAR NEUROBIOLOGY 38.4(2018):929-939. |
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。