Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ2

被引:75
作者
Tarun K Garg
Jason Y Chang
机构
[1] Department of Anatomy, Univ. of Arkansas for Med. Sciences, Little Rock
[2] Department of Ophthalmology, Univ. of Arkansas for Med. Sciences, Little Rock
关键词
Retinal Pigment Epithelium; Retinal Pigment Epithelium Cell; H2O2 Treatment; Photoreceptor Outer Segment; Human Retinal Pigment Epithelium Cell;
D O I
10.1186/1471-2415-3-5
中图分类号
学科分类号
摘要
Background: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H2O2) induced)oxidative stress on retinal pigment epithelium were characterized in this study. Methods: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. Results: The treatment of retinal pigment epithelial cells with (H2O2 caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ 2 and by the protein kinase inhibitor, AG126. Conclusion: 15d-PGJ2 and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases.
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页码:1 / 15
页数:14
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共 67 条
[1]  
Rozanowska M., Jarvis-Evans J., Korytowski W., Boulton M.E., Burke J.M., Sarna T., Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species, J. Biol. Chem., 270, pp. 18825-18830, (1995)
[2]  
Miceli M.V., Liles M.R., Newsome D.A., Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis, Exp. Cell Res., 214, pp. 242-249, (1994)
[3]  
Tate Jr. D.J., Miceli M.V., Newsome D.A., Phagocytosis and H2O2 induce catalase and metallothionein gene expression in human retinal pigment epithelial cells, Invest. Ophthalmol. Vis. Sci., 36, pp. 1271-1279, (1995)
[4]  
Cai J., Nelson K.C., Wu M., Sternberg Jr. P., Jones D.P., Oxidative damage and protection of the RPE, Prog. Retin. Eye Res., 19, pp. 205-221, (2000)
[5]  
Winkler B.S., Boulton M.E., Gottsch J.D., Sternberg P., Oxidative damage and age-related macular degeneration, Mol. Vis., 5, pp. 32-42, (1999)
[6]  
Wills N.K., Weng T., Mo L., Hellmich H.L., Yu A., Wang T., Buchheit S., Godley B.F., Chloride channel expression in cultured human fetal RPE cells: Response to oxidative stress, Invest. Ophthalmol. Vis. Sci., 41, pp. 4247-4255, (2000)
[7]  
Jahngen-Hodge J., Obin M.S., Gong X., Shang F., Nowell Jr. T.R., Gong J., Abasi H., Blumberg J., Taylor A., Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress, J. Biol. Chem., 272, pp. 28218-28226, (1997)
[8]  
Barak A., Morse L.S., Goldkorn T., Ceramide: A potential mediator of apoptosis in human retinal pigment epithelial cells, Invest. Ophthalmol. Vis. Sci., 42, pp. 247-254, (2001)
[9]  
Tate D.J., Miceli M.V., Newsome D.A., Zinc protects against oxidative damage in cultured human retinal pigment epithelial cells, Free Radic. Biol. Med., 26, pp. 704-713, (1999)
[10]  
Ballinger S.W., Van Houten B., Jin G.F., Conklin C.A., Godley B.F., Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells, Exp. Eye. Res., 68, pp. 765-772, (1999)