Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

doi:10.1038/aps.2009.80

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	Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro
	Xie, Ke-qiang 2; Zhang, Li-min 2; Cao, Yan 2; Zhu, Jun 1; Feng, Lin-yin2
刊名	ACTA PHARMACOLOGICA SINICA
	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.
资助项目	National Basic Research Program of China[2007CB935804]
WOS关键词	EPIDERMAL-GROWTH-FACTOR ; PROTEIN-COUPLED RECEPTORS ; KINASE-B ; PHOSPHOINOSITIDE 3-KINASE ; SIGNALING PATHWAY ; ANGIOTENSIN-II ; PC12 CELLS ; ACTIVATION ; MECHANISMS ; PHOSPHORYLATION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3628662
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000268066400002
内容类型	期刊论文
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.