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E. Chaum, J. Yin, W. Huo, J. C. Lang; Studies of Zinc and Vitamin C Modulation of AP-1 Gene Regulation in the Human Retinal Pigment Epithelium Under Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1428.
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We have previously shown that oxidative stress (OS) can quantitatively regulate AP-1 gene expression changes and that pretreatment with specific doses of vitamin C alone, in vitro, may play an important protective role in the human retinal pigment epithelium (RPE) under conditions of OS. Other micronutrients, specifically dietary zinc, have been shown to reduce the risk of progression of age-related macular degeneration in the AREDS clinical trials. The purpose of this study was to determine whether AP-1 biomarker responses to quantified levels of OS are modulated by pretreatment with zinc alone and if zinc supplementation can synergistically enhance the protective effects of vitamin C pretreatment in vitro.
Confluent ARPE-19 cells were cultured for three days in defined media in the presence of zinc (0 - 60µM) alone, or zinc with vitamin C (100 and 200µM), and then treated for 1 hour with 500µM H2O2. RNA was isolated using a no-rinse method at 0-, 1-, 4-, 8-, and 24-hours after OS and compared to untreated controls at each time point. AP-1 family genes FosB, cFos, JunB, ATF3, and EGR2 transcription factor gene expression was determined by quantitative PCR.
Zinc pretreatment alone, or in combination with vitamin C, did not alter AP-1 family or EGR2 gene expression in response to OS compared with the controls. Alternative transcription factor and zinc-coenzyme pathways that may play a role in mediating the clinically protective responses to zinc are being evaluated and will be presented at the meeting.
Unlike vitamin C, the protective effects of zinc supplementation seen in the AREDS clinical studies do not appear to be mediated directly through AP-1 transcription factors under experimental conditions of acute OS in the human RPE.
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