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Y. S. Yu, J. Kim, J. Kim, B. Min, K.-W. Kim; Clusterin Protects Human Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Apoptosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1418.
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The oxidative stress to retinal pigment epithelial (RPE) cell is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study is to investigate whether clusterin protects human RPE cells from ROS-induced apoptosis through PI3K/Akt survival pathway.
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 PI3K/Akt pathway was determined by Western blot analysis.
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 abrogation of apoptotic bodies. Interestingly, clusterin induced Akt phosphorylation in human RPE cells under oxidative stress, which contributed to cellular viability in ARPE-19 cells. This cellular survival by clusterin was blocked by a PI3K inhibitor.
Clusterin may play a protective role in responding to the local redox environment of human RPE cells, which contributes to the cellular survival via PI3K/Akt pathway. Therefore, clusterin couldd be considered for the preventive approach to AMD.
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