Oxidative stress affects retinal pigment epithelial cell survival through epidermal growth factor receptor/AKT signaling pathway
| Autor: | Taotao Chen, Ming-Yang Su, Hai-Yan Hong, Xiao Dong Chen, Wensheng Li, Aidong Han |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
03 medical and health sciences lcsh:Ophthalmology Epidermal growth factor oxidative stress Medicine Viability assay Epidermal growth factor receptor Protein kinase B PI3K/AKT/mTOR pathway biology Akt/PKB signaling pathway Cell growth business.industry AKT retinal pigment epithelial cell Ophthalmology 030104 developmental biology Basic Research lcsh:RE1-994 Cancer research biology.protein Phosphorylation epidermal growth factor receptor business |
| Zdroj: | International Journal of Ophthalmology, Vol 10, Iss 4, Pp 507-514 (2017) |
| ISSN: | 2222-3959 |
| Popis: | Aim To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial (RPE) cells. Methods Human RPE cell lines (ARPE-19 cell) were treated with different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2). Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay. EGFR/AKT signaling was detected by Western blot. EGFR localization was also detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK-2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine (NAC). Results EGF treatment increased ARPE-19 cell viability and proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through alleviating reduction of EGFR, and phosphorylated and total AKT proteins. Conclusion Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction. |
| Databáze: | OpenAIRE |
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