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S. R. Sripathi, S. Marwana, Z. Liu, T. Moser, E. Hager, W. Jahng; Erythropoietin Interaction Network Under the Redox Imbalance Condition. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1682.
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The mechanisms to regulate the expression of proteins that protect against light-induced oxidative stress remain elusive. Altered cGMP concentration, increased permeability of cation channels, up-regulated Ca2+ concentration, oxidative damage, perturbed levels of specific amino acids, changes in energy metabolism have been proposed to be involved in light-induced retina degeneration. We suggest that oxygen-imbalance conditions such as exposure to constant light, production of reactive oxygen species, hypoxic, and hyperoxic environment may regulate protection mechanism of retinal and RPE cells through erythropoietin (EPO) by anti-apoptotic signaling. We investigate whether the EPO-dependent pathway is up regulated in the retina and RPE in various oxygen-imbalance conditions. The possible connections of EPO regulation in relation to light via downstream regulators are investigated.
Bioinformatic analysis using computational methods implies possible connections of EPO regulators. Extensive biochemical studies such as immunoprecipitation, gel electrophoresis, Western blot and post-translational modification search have revealed EPO interaction network under oxidative stress condition.
We found out the up-regulation of EPO and its receptor (EPOR), and changes of downstream signaling molecules under oxidative stress. Among these, increase of p-STAT3, Prx2, Mn-SOD, NF-kB, and VEGFR signaling are connected directly or indirectly with EPO. Down-regulations of Beclin1, Prx1, and caspase 3 are observed under the specific oxidative stress condition.
EPO interaction network might play an important role in the protection of retinal neurons during the daytime or during highly oxidative stress conditions such as continuous light exposure. Induction of EPO expression by light exposure and positive correlations of down-stream regulators may represent its functional role in the light.
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