anovelgsk3inhibitoryq138preventsneuronalinjuryinducedbyglutamateandbrainischemiathroughactivationofthenrf2signalingpathway
文献类型：期刊论文
| 作者 | Pang Tao1; Wang Yunjie1; Gao Yuanxue1; Xu Yuan1; Li Qiu2; Zhou Yubo3 ; Xu Lei3; Huang Zhangjian1; Liao Hong1; Zhang Luyong1
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| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2016 |
| 卷号 | 000期号:006页码:741 |
| 关键词 | 神经元损伤 酶抑制剂 谷氨酸 脑缺血 诱导 信号通路 神经保护作用 β-catenin |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim： To discover neuroprotective compounds and to characterize the discovered active compound YQ138 as a novel GSK-313 inhibitor. Methods： Primary rat cerebellar granule cells （CGCs） were treated with glutamate, and cell viability was analyzed with MTT assay, which was used as in vitro model for screening neuroprotective compounds. Active compound was further tested in OGD- or serum deprivation-induced neuronal injury models. The expression levels of GSK-313 downstream proteins （Nrf2, HO-1, NQ01, Tau and （3-catenin） were detected with Western blotting. For evaluating the neuroprotective effects in vivo, adult male rats were subjected to transient middle cerebral artery occlusion （tMCAO）, then treated with YQ138 （10 mg/kg, iv） at 2, 4 and 6 h after ischemia onset. Results： From a compound library consisting of about 2000 potential kinase inhibitors, YQ138 was found to exert neuroprotective effects： pretreatment with YQ138 （0.1-40 pmol/L） dose-dependently inhibited glutamate-induced neuronal death. Furthermore, pretreatment with YQ138 （10 pmol/L） significantly inhibited OGD- or serum deprivation-induced neuronal death. Among a panel of seven kinases tested, YQ138 selectively inhibited the activity of GSK-313 （ICso=0.52 nmol/L）. Furthermore, YQ138 dose-dependently increased the expression of 13-catenin, and decreased the phosphorylation of Tau in CGCs. Moreover, YQ138 significantly increased the expression of GSK-313 downstream antioxidative proteins Nrf2, HO-1, NQ01, GSH and SOD in CGCs. In rats with tMCAO, administration of YQ138 significantly decreased infarct volume, improved the neurological deficit, and increased the expression of Nrf2 and HO-1 and the activities of SOD and GSH in the cerebral cortex. Conclusion： A novel GSK-313 inhibitor YQ138 effectively suppresses brain ischemic injury in vitro and in vivo. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288299]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国药科大学 2.浙江工业大学 3.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Pang Tao,Wang Yunjie,Gao Yuanxue,et al. anovelgsk3inhibitoryq138preventsneuronalinjuryinducedbyglutamateandbrainischemiathroughactivationofthenrf2signalingpathway[J]. actapharmacologicasinica,2016,000(006):741. |
| APA | Pang Tao.,Wang Yunjie.,Gao Yuanxue.,Xu Yuan.,Li Qiu.,...&Li Jia.(2016).anovelgsk3inhibitoryq138preventsneuronalinjuryinducedbyglutamateandbrainischemiathroughactivationofthenrf2signalingpathway.actapharmacologicasinica,000(006),741. |
| MLA | Pang Tao,et al."anovelgsk3inhibitoryq138preventsneuronalinjuryinducedbyglutamateandbrainischemiathroughactivationofthenrf2signalingpathway".actapharmacologicasinica 000.006(2016):741. |
入库方式： OAI收割
来源：上海药物研究所
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