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Kristen Buehne, Ping Yang, Glenn Jaffe; Effects of resveratrol and hydroquinone on the endoplasmic reticulum and mitochondria in human RPE cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4034.
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Progression of age-related macular degeneration (AMD) is linked to an increase in cell endoplasmic reticulum (ER) and mitochondrial stress. Studies suggest that resveratrol has varying effects on cell survival depending on experimental conditions; this drug is reported to induce not only antioxidant, but also pro-apoptotic behaviors among different cell types. To better understand the effects of resveratrol in RPE cells exposed to oxidative stress, we investigated the effects of this drug on cell viability, mitochondrial DNA, and C/EBP homologous protein (CHOP), an ER stress protein, in RPE cells subjected to hydroquinone, an environmental toxin and cellular stressor.
Cultured human RPE cells were pretreated with resveratrol (30uM) for 24 hours. Cells were then treated with hydroquinone at various concentrations (75-125uM) for 2 or 5 hours. Cell morphology was assessed by light microscopy. Cell viability was determined with WST-1 reagent. Mitochondrial DNA levels were evaluated by quantitative PCR. CHOP protein levels were evaluated by Western blot.
In the presence of hydroquinone, resveratrol-treated cells exhibited altered morphology when compared to untreated cells. This finding was associated with greater cell viability among resveratrol-treated cells, as measured by WST-1 reagent. Hydroquinone increased levels of CHOP when compared to untreated cells. Comparatively, lower amounts of this protein were seen in cells pre-treated with resveratrol. Resveratrol-treated cells had lower levels of mitochondrial DNA when in combination with hydroquinone treatments.
Resveratrol improves the viability of RPE cells exposed to hydroquinone, and decreases CHOP protein levels. Resveratrol also reduces the amount of mitochondrial DNA. These data imply that resveratrol has complex biological effects on RPE cells exposed to oxidative stress, which could explain the multiple behaviors exhibited by this drug. This study helps clarify the role of resveratrol to limit oxidant injury in RPE cells and in future treatments for AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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