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• W3093960235 abstract "7-ketocholesterol (7kCh), a natural byproduct of oxidation in lipoprotein deposits is implicated in the pathogenesis of diabetic retinopathy and age-related macular degeneration (AMD). This study was performed to investigate whether several clinical drugs can inhibit 7kCh-induced caspase activation and mitigate its apoptotic effects on retinal cells in vitro.Two populations of retinal cells, human retinal pigment epithelial cells (ARPE-19) and rat neuroretinal cells (R28) were exposed to 7kCh in the presence of the following inhibitors: Z-VAD-FMK (pan-caspase inhibitor), simvastatin, memantine, epicatechin, and Z-IETD-FMK (caspase-8 inhibitor) or Z-ATAD-FMK (caspase-12 inhibitor). Caspase-3/7, -8, and -12 activity levels were measured by fluorochrome caspase assays to quantify cell death. IncuCyte live-cell microscopic images were obtained to quantify cell counts.Exposure to 7kCh for 24 hours significantly increased caspase activities for both ARPE-19 and R28 cells (P< 0.05). In ARPE cells, pretreatment with various drugs had significantly lower caspase-3/7, -8, and -12 activities, reported in % change in mean signal intensity (msi): Z-VAD-FMK (48% decrease, P< 0.01), memantine (decreased 47.8% at 1 µM, P = 0.0039 and 81.9% at 1 mM, P< 0.001), simvastatin (decreased 85.3% at 0.01 µM, P< 0.001 and 84.8% at 0.05 µM, P< 0.001) or epicatechin (83.6% decrease, P< 0.05), Z-IETD-FMK (68.1% decrease, P< 0.01), and Z-ATAD-FMK (47.7% decrease, P = 0.0017). In contrast, R28 cells exposed to 7kCh continued to have elevated caspase-3/7, -8, and -12 activities (between 25.7% decrease and 17.5% increase in msi, P> 0.05) regardless of the pretreatment.Several current drugs protect ARPE-19 cells but not R28 cells from 7kCh-induced apoptosis, suggesting that a multiple-drug approach is needed to protect both cells types in various retinal diseases." @default.
• W3093960235 created "2020-10-29" @default.
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• W3093960235 date "2020-10-25" @default.
• W3093960235 modified "2023-10-18" @default.
• W3093960235 title "Memantine, Simvastatin, and Epicatechin Inhibit 7-Ketocholesterol-induced Apoptosis in Retinal Pigment Epithelial Cells But Not Neurosensory Retinal Cells In Vitro" @default.
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• W3093960235 doi "https://doi.org/10.18502/jovr.v15i4.7781" @default.
• W3093960235 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7591846" @default.
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• W3093960235 hasPublicationYear "2020" @default.
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