Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 46, Issue 8, Pages 1032-1041Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.11.027
Keywords
Apoptosis; Erythropoietin; Mitochondria; Oxidant stress; Free radicals
Funding
- Zhejiang Foundation of Natural Sciences
- National Basic Research Program [2006CB503909]
- Wenzhou bureau of science and technology [Y2004A713]
- Zhejiang youth foundation of traditional Chinese medicine [2005Y042]
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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-a and interleukin-1 beta, 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 H2O2 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. (C) 2008 Elsevier Inc. All rights reserved.
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