Protective effect of clusterin from oxidative stress-induced apoptosis in human retinal pigment epithelial cells

Jeong Hun Kim, Jin Hyoung Kim, Hyoung Oh Jun, Young Suk Yu, Bon Hong Min, Kyu Hyung Park, Kyu Won Kim

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57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)561-566
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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