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Protective Effect of Clusterin from Oxidative Stress-Induced Apoptosis in Human Retinal Pigment Epithelial Cells

Authors
Kim, Jeong HunKim, Jin HyoungJun, Hyoung OhYu, Young SukMin, Bon HongPark, Kyu HyungKim, Kyu-Won
Issue Date
1월-2010
Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Citation
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.51, no.1, pp.561 - 566
Indexed
SCIE
SCOPUS
Journal Title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume
51
Number
1
Start Page
561
End Page
566
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/117207
DOI
10.1167/iovs.09-3774
ISSN
0146-0404
Abstract
PURPOSE. Oxidative stress to retinal pigment epithelial (RPE) cells is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study was conducted to investigate whether clusterin protects human RPE cells from ROS-induced apoptosis through a PI3K/Akt survival pathway. METHODS. The preventive effect of clusterin on reactive oxygen species (ROS) production and RPE cell death induced by hydrogen peroxide was determined in ARPE-19 cells. The ability of clusterin to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and DAPI staining. Furthermore, the protective effect of clusterin via the PI3K/Akt pathway was determined by Western blot analysis. RESULTS. Clusterin prevented ARPE-19 cells from H2O2-induced cell death and ROS production. H2O2-induced oxidative stress increased caspase-3 activity, which was significantly inhibited by clusterin, as determined by the abrogation of apoptotic bodies. Interestingly, clusterin induced Akt phosphorylation in human RPE cells under oxidative stress, which contributed to cell viability in ARPE-19 cells. This cell survival by clusterin was blocked by a PI3K inhibitor. CONCLUSIONS. Clusterin may play a protective role in responding to the local redox environment of human RPE cells, which contributes to the cell survival via the PI3K/Akt pathway. Therefore, clusterin could be considered for the preventive approach to AMD. (Invest Ophthalmol Vis Sci. 2010;51:561-566) DOI:10.1167/iovs.09-3774
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