Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro
文献类型：期刊论文
| 作者 | Xie, Ke-qiang2; Zhang, Li-min2; Cao, Yan2; Zhu, Jun1; Feng, Lin-yin2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2009-07 |
| 卷号 | 30期号:7页码:889-898 |
| 关键词 | adenosine A(1) receptor epidermal growth factor receptor transactivation Akt Src kinase ERK1/2 G(i) protein metalloprotease PI3K |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2009.80 |
| 文献子类 | Article |
| 英文摘要 | Aim: To understand the mechanism of the transactivation of the epidermal growth factor receptor (EGFR) mediated by the adenosine A(1) receptor (A(1)R). Methods: Primary cultured rat cortical neurons subjected to oxygen-glucose deprivation (OGD) and HEK293/A(1)R cells were treated with the A(1)R-specific agonist N-6-cyclopentyladenosine (CPA). Phospho-EGFR, Akt, and ERK1/2 were observed by Western blot. An interaction between EGFR and A(1)R was detected using immunoprecipitation and immunocytochemistry. Results: The A(1)R agonist CPA causes protein kinase B (Akt) activation and protects primary cortical neurons from oxygen-glucose deprivation (OGD) insult. A(1)R and EGFR co-localize in the membranes of neurons and form an immunocomplex. A(1)R stimulation induces significant EGFR phosphorylation via a PI3K and Src kinase signaling pathway; this stimulation provides a neuroprotective effect in cortical neurons. CPA leads to sustained phosphorylation of extracellularly regulated kinases 1 and 2 (ERK1/2) in cortical neurons, but only to transient phosphorylation in HEK 293/A(1)R cells. The response to the A(1)R agonist is mediated primarily through EGFR transactivation that is dependent on pertussis toxin (PTX)-sensitive G(i) protein and metalloproteases in HEK 293/A(1)R. Conclusion: A(1)R-mediated EGFR transactivation confers a neuroprotective effect in primary cortical neurons. PI3 kinase and Src kinase play pivotal roles in this response. |
| WOS关键词 | EPIDERMAL-GROWTH-FACTOR ; PROTEIN-COUPLED RECEPTORS ; KINASE-B ; PHOSPHOINOSITIDE 3-KINASE ; SIGNALING PATHWAY ; ANGIOTENSIN-II ; PC12 CELLS ; ACTIVATION ; MECHANISMS ; PHOSPHORYLATION |
| 资助项目 | National Basic Research Program of China[2007CB935804] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3628662 |
| WOS记录号 | WOS:000268066400002 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279189]  |
| 专题 | 药理学第二研究室 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 |
| 通讯作者 | Feng, Lin-yin |
| 作者单位 | 1.Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Neuropharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xie, Ke-qiang,Zhang, Li-min,Cao, Yan,et al. Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro[J]. ACTA PHARMACOLOGICA SINICA,2009,30(7):889-898. |
| APA | Xie, Ke-qiang,Zhang, Li-min,Cao, Yan,Zhu, Jun,&Feng, Lin-yin.(2009).Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro.ACTA PHARMACOLOGICA SINICA,30(7),889-898. |
| MLA | Xie, Ke-qiang,et al."Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro".ACTA PHARMACOLOGICA SINICA 30.7(2009):889-898. |
入库方式： OAI收割
来源：上海药物研究所
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