Pigment epithelium-derived factor inhibits oxidative stress-induced cell death by activation of extracellular signal-regulated kinases in cultured retinal pigment epithelial cells |
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Authors: | Tsao Yeou-Ping Ho Tsung-Chuan Chen Show-Li Cheng Huey-Chuan |
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Affiliation: | Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan. yptsao@yahoo.com |
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Abstract: | Oxidative stress-induced retinal pigment epithelial (RPE) cell death is involved in the pathogenesis of age-related macular degeneration (AMD). Pigment epithelium-derived factor (PEDF) is an anti-angiogenic/neurotropic dual functional factor, and recently it was also shown to mediate anti-oxidative action. In the present study, the influence of PEDF in hydrogen peroxide (H(2)O(2))-induced RPE cell death was investigated using nontransformed human RPE cell line (ARPE-19). The recombinant PEDF was purified from E. coli. The MTT cell viability assay showed that PEDF rescued ARPE-19 from H(2)O(2)-induced cell death in a dose- and time-dependent manner. Western blot analysis revealed that PEDF stimulated the extracellular signal-regulated kinases (ERK1/2) phosphorylation. The PEDF cytoprotective effect was significantly attenuated by the ERK1/2 inhibitor PD98059. In this study, we demonstrate that PEDF induces ERK1/2 phosphorylation and we further suggest that the ERK signal cascade contributes to RPE cell's cytoprotection against oxidative stress. |
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Keywords: | PEDF Oxidative stress RPE ARPE-19 ERK1/2 |
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