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L. Gong, M. Deng, S. Sun, H. Feng, Y.-M. Xiao, D. W. Li; Oxidative Stress Activates Multiple Signaling Pathways to Induce Apoptosis of Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5056.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress is implicated in many pathological processes including retinal diseases. In the present study, we have explored the signaling pathways activated by oxidative stress in retinal pigment epithelial cells (ARPE-19) in culture.
ARPE-19 cells were cultured in MEM. Constant hydrogen peroxide was maintained in the culture media. After treatment, the mock and treated cells were harvested for analysis of gene expression, kinase activation and apoptosis through RT-PCR, Western blot, Electron microscopy and Hochst staining.
Under treatment of a constant level of 90 uM hydrogen peroxide, the ARPE-19 cells were induced to undergo apoptosis. Mechanistically, in contrast to the response to the lower level of hydrogen peroxide (50 uM), the treated ARPE-19 cells were induced to activate three major MAP kinases: ERK1/2, JNK1/2 and p38 kinases, followed by hyperphosphorylation of p53 at serine-15 residue and activation of caspase-9 and caspase-8, key caspases of the mitochondrial death pathway and extrinsic death pathway, respectively. In addition, hydrogen peroxide also downregulated expression of the protein serine/threonine phosphatase-1 and -2A to enhance apoptosis of the ARPE-19 cells.
Oxidative stress may regulate multiple signaling pathways to initiate pathological processes in retinal pigment epithelial cells.
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