Preprint Article Version 1 This version is not peer-reviewed

Resveratrol Restores LINE-1 Methylation Levels by Modulating SIRT1 and DNMTs Functions in Cellular Models of Age-Related Macular Degeneration

Version 1 : Received: 25 May 2018 / Approved: 28 May 2018 / Online: 28 May 2018 (10:33:13 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2018, 19, 2118
DOI: 10.3390/ijms19072118

Abstract

The role of epigenetic alterations in the pathogenesis of 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 restore changes in LINE-1 methylation by modulating DNMTs and SIRT1 functions. 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<0.0001). We also demonstrated that treatment with 10 μM resveratrol for 24 hours counteracted the detrimental effect on LINE-1 methylation via increasing DNMTs and SIRT1 functions in cells upon oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of AMD.

Subject Areas

retinal degeneration; DNA methylation; epigenetics; oxidative stress; inflammation

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.