Ke-Qiang Xie1, Li-Min Zhang, Yan Cao, Jun Zhu, Lin-Yin Feng. 1. State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract
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.Acta Pharmacologica Sinica (2009) 30: 889-898; doi: 10.1038/aps.2009.80.
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.Acta Pharmacologica Sinica (2009) 30: 889-898; doi: 10.1038/aps.2009.80.
Authors: Arti Shukla; Trisha F Barrett; Maximilian B MacPherson; Jedd M Hillegass; Naomi K Fukagawa; William A Swain; Kenneth J O'Byrne; Joseph R Testa; Harvey I Pass; Stephen P Faux; Brooke T Mossman Journal: Am J Respir Cell Mol Biol Date: 2011-03-31 Impact factor: 6.914
Authors: Jian Zhou; Martha B Alvarez-Elizondo; Elliot Botvinick; Steven C George Journal: Am J Respir Cell Mol Biol Date: 2012-12-06 Impact factor: 6.914
Authors: Phuc N H Trinh; Jo-Anne Baltos; Shane D Hellyer; Lauren T May; Karen J Gregory Journal: Purinergic Signal Date: 2022-07-23 Impact factor: 3.950
Authors: Paul G W Keddy; Kate Dunlop; Jordan Warford; Michel L Samson; Quinton R D Jones; H P Vasantha Rupasinghe; George S Robertson Journal: PLoS One Date: 2012-12-12 Impact factor: 3.240