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Jinggang Yin, Weihong Huo, J.C. Lang, Edward Chaum; Synergistic Effects of Vitamin E and Vitamin C Modulation of AP-1 Gene Regulation in the Human Retinal Pigment Epithelium Under Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4430.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that pretreatment with specific doses of vitamin C can protect the RPE by modulating oxidative stress-induced (OS) AP-1 gene expression in ARPE-19 cells. Other antioxidant micronutrients, especially vitamin E, have been shown to confer protective antioxidant effects in non-retinal cell-lines. The purpose of present study was to determine whether vitamin E can synergistically enhance the protective effects of vitamin C against OS using an in vitro biomarker assay.
Confluent ARPE-19 cells were cultured for three days in defined media in the presence of vitamin E (50µM) with vitamin C (50, 100, or 200µM), and then treated for 1 hour with 500µM H2O2. RNA was isolated at 0-, 1-, 4-, 8-, and 24-hours after OS and compared to untreated controls at each time point. Transcription factor gene expression, in particular the AP-1 genes (FosB, cFos, and ATF3), EGR1/2, and the antioxidant gene HO-1 was determined by real-time PCR.
The characteristic OS response seen in AP-1, EGR2, and HO-1 gene expression was reduced in cells pretreated with vitamin E and vitamin C cells. FosB gene expression was reduced by ~91% and 86% (from 38.5-fold to 3.4-fold, and from 12.8-fold to 1.6-fold ) under OS in the presence of 50µM vitamin E and 100µM vitamin C. ATF3 gene expression was reduced ~24% and ~58% at 1-, and 8-hours after OS, respectively, and EGR2 gene expression was reduced ~85% and ~73% at 1-, and 8-hours after OS, respectively. Similarly, HO-1 transcription was reduced more than 70% after 24 hours following OS when pretreated with both vitamin E and vitamin C.
Vitamin E supplementation in conjunction with vitamin C pretreatment modulates the expression of AP-1 biomarkers, EGR2, and HO-1 in RPE cells under oxidative stress. Vitamin E at 50µM synergistically enhances the protective effects of lower concentrations of vitamin C in the RPE cells by reducing OS-responses that may trigger apoptosis.
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