期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms19072118
关键词
retinal degeneration; DNA methylation; epigenetics; oxidative stress; inflammation
资金
- Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia, Universita di Catania (Piano Triennale di Sviluppo delle Attivita di Ricerca Scientifica del Dipartimento)
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 mu g/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 mu M 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.
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