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Open AccessArticle

Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation

1
Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy
2
SIFI SpA, Research and Development Department, Via Ercole Patti 36, 95025 Catania, Italy
3
Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Plebiscito, 628, 95124 Catania, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 2118; https://doi.org/10.3390/ijms19072118
Received: 25 May 2018 / Revised: 14 July 2018 / Accepted: 17 July 2018 / Published: 20 July 2018
(This article belongs to the Special Issue Nutrition, Epigenetics, and Diseases)
The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, including age-related macular degeneration (AMD), has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may modulate DNMT and SIRT1 functions and restore changes in LINE-1 methylation. Cells were treated with 25 mU/mL glucose oxidase (GOx) or 10 µg/mL lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b, and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−28.5%; p < 0.0001) and SIRT1 (−29.0%; p < 0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−14.9%; p = 0.007) and SIRT1 (−20.1%; p < 0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values < 0.001). We also demonstrated that treatment with 10 μM resveratrol for 24 h counteracted the detrimental effect on DNMT and SIRT1 functions, and LINE-1 methylation, in cells under oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of retinal degenerative diseases. View Full-Text
Keywords: retinal degeneration; DNA methylation; epigenetics; oxidative stress; inflammation retinal degeneration; DNA methylation; epigenetics; oxidative stress; inflammation
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MDPI and ACS Style

Maugeri, A.; Barchitta, M.; Mazzone, M.G.; Giuliano, F.; Basile, G.; Agodi, A. Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation. Int. J. Mol. Sci. 2018, 19, 2118. https://doi.org/10.3390/ijms19072118

AMA Style

Maugeri A, Barchitta M, Mazzone MG, Giuliano F, Basile G, Agodi A. Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation. International Journal of Molecular Sciences. 2018; 19(7):2118. https://doi.org/10.3390/ijms19072118

Chicago/Turabian Style

Maugeri, Andrea; Barchitta, Martina; Mazzone, Maria G.; Giuliano, Francesco; Basile, Guido; Agodi, Antonella. 2018. "Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation" Int. J. Mol. Sci. 19, no. 7: 2118. https://doi.org/10.3390/ijms19072118

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