Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A(1) receptor-mediated transactivation of epidermal growth factor receptor
文献类型:期刊论文
作者 | Zhong, Min; Song, Wan-ling; Xu, Ye-chun![]() ![]() ![]() |
刊名 | ACTA PHARMACOLOGICA SINICA
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出版日期 | 2015-03 |
卷号 | 36期号:3页码:298-310 |
关键词 | paeoniflorin Chinese herb cortical neurons oxygen-glucose deprivation neuroprotection adenosine A(1) receptor EGFR transactivation wortmannin U0126 DPCPX AG1478 PP2 BiPs |
ISSN号 | 1671-4083 |
DOI | 10.1038/aps.2014.154 |
文献子类 | Article |
英文摘要 | Aim: Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons. Methods: Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A(1)R (HEK293/A(1)R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining. Results: Paeoniflorin (10 nmol/L to 1 mu mol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A(1)R cells. Both A(1)R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A(1)R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A(1)R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorin-induced phosphorylation of ERK1/2 (and Akt) in HEK293/A(1)R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. Conclusion: Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A(1)R-mediated transactivation of EGFR. |
WOS关键词 | PROTEIN-COUPLED RECEPTORS ; REPERFUSION INJURY ; ISCHEMIA/REPERFUSION INJURY ; CEREBRAL-ISCHEMIA ; ACTIVATION ; RATS ; PATHWAY ; CELLS ; PERFORMANCE ; SUPPRESSES |
资助项目 | National Natural Science Foundation of China[81123004] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA 01040304] |
WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
语种 | 英语 |
CSCD记录号 | CSCD:5386857 |
WOS记录号 | WOS:000351173700002 |
出版者 | ACTA PHARMACOLOGICA SINICA |
源URL | [http://119.78.100.183/handle/2S10ELR8/276619] ![]() |
专题 | 药理学第二研究室 |
通讯作者 | Feng, Lin-yin |
作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Zhong, Min,Song, Wan-ling,Xu, Ye-chun,et al. Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A(1) receptor-mediated transactivation of epidermal growth factor receptor[J]. ACTA PHARMACOLOGICA SINICA,2015,36(3):298-310. |
APA | Zhong, Min,Song, Wan-ling,Xu, Ye-chun,Ye, Yang,&Feng, Lin-yin.(2015).Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A(1) receptor-mediated transactivation of epidermal growth factor receptor.ACTA PHARMACOLOGICA SINICA,36(3),298-310. |
MLA | Zhong, Min,et al."Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A(1) receptor-mediated transactivation of epidermal growth factor receptor".ACTA PHARMACOLOGICA SINICA 36.3(2015):298-310. |
入库方式: OAI收割
来源:上海药物研究所
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