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Seung Jin Noh, Woo Jin Jeong, Jee Hyun Rho, Dong Min Shin, Hee Bae Ahn, Woo Chan Park, Sae Heun Rho, Young Hwa Soung, Tae Hyun Kim, Bong Soo Park, Young Hyun Yoo; Sensitization of RPE Cells by αB-Crystallin siRNA to SAHA-Induced Stage 1 Apoptosis through Abolishing the Association of αB-Crystallin with HDAC1 in SC35 Speckles. Invest. Ophthalmol. Vis. Sci. 2008;49(11):4753-4759. doi: 10.1167/iovs.08-2166.
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purpose. To better understand the mechanism underlying the anti-apoptotic activity of αB-crystallin in RPE cells.
methods. Cells of the human retinal pigment epithelial line ARPE-19 were treated with a histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), with or without αB-crystallin siRNA. To examine the mechanism underlying the cell death induced in ARPE-19 cells, nuclear staining, flow cytometry, DNA electrophoresis, pulse field gel electrophoresis, Western blot analysis, confocal microscopy, and coimmunoprecipitation assay were undertaken.
results. The present study demonstrated that an HDACI, SAHA, at the usual doses or the silencing of αB-crystallin by siRNA alone did not effectively induce apoptosis in ARPE-19 cells. Silencing of αB-crystallin likely abolishes the anti-apoptotic activity of αB-crystallin. The data indicated that silencing of αB-crystallin sensitizes ARPE19 cells to SAHA-induced apoptosis and leads them to stage 1 apoptosis. αB-Crystallin associates with HDAC1 on SC35 speckles, and silencing of αB-crystallin abolishes this association, resulting in the induction of apoptosis. The data indicated that the association between αB-crystallin and HDAC1 on SC35 speckles plays a pivotal role in anti-apoptotic activity.
conclusions. Knockout of αB-crystallin may be a promising new approach to enhance therapeutic potency for proliferative vitreoretinopathy without compromising efficacy.
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