Pigment epithelium-derived factor inhibits oxidative stress-induced cell death by activation of extracellular signal-regulated kinases in cultured retinal pigment epithelial cells.
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.
Tsao
Yeou-Ping
YP
Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan. yptsao@yahoo.com
Ho
Tsung-Chuan
TC
Chen
Show-Li
SL
Cheng
Huey-Chuan
HC
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005136:Eye Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015843:Serpins / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D000099174:Pigment Epithelium-Derived Factor
D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005136:Eye Proteins; D006861:Hydrogen Peroxide; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor