Erythropoietin protects retinal pigment epithelial cells from oxidative damage.
Oxidative damage from reactive oxygen species (ROS) has been implicated in many diseases, including age-related macular degeneration, in which the retinal pigment epithelium (RPE) is considered a primary target. The aim of this study was to determine whether erythropoietin (EPO) protects cultured human RPE cells against oxidative damage and to identify the pathways that may mediate protection. EPO (1 IU/ml) significantly increased the viability of oxidant-treated RPE cells, decreased the release of the inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, recovered the RPE cells' barrier integrity disrupted by oxidative stress, prevented oxidant-induced cell DNA fragmentation and membrane phosphatidylserine exposure, and also reduced the levels of oxidant-induced intracellular ROS and restored cellular antioxidant potential, total antioxidant capacity, glutathione peroxidase, and superoxide dismutase and decreased malondialdehyde, the end product of lipid peroxidation. EPO inhibited caspase-3-like activity. Protection by EPO was partly dependent on the activation of Akt1 and the maintenance of the mitochondrial membrane potential. No enhanced or synergistic protection was observed during application of Z-DEVD-FMK (caspase-3 inhibitor) combined with EPO compared with cultures exposed to EPO and H(2)O(2) alone. Together, these results suggest that EPO could protect against oxidative injury-induced cell death and mitochondrial dysfunction in RPE cells through modulation of Akt1 phosphorylation, mitochondrial membrane potential, and cysteine protease activity.
Wang
Zhao-yang
ZY
The School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
Shen
Li-jun
LJ
Tu
Lili
L
Hu
Dan-ning
DN
Liu
Guo-Ying
GY
Zhou
Zhong-lou
ZL
Lin
Yi
Y
Chen
Lin-Hua
LH
Qu
Jia
J
D000375:Aging / Q000473:pathology / Q000502:physiology*; D017209:Apoptosis; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008268:Macular Degeneration / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D061945:Caspase Inhibitors; D053583:Interleukin-1beta; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D004921:Erythropoietin; D013482:Superoxide Dismutase; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D003546:Cysteine Endopeptidases