Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery

• Published in: Oxidative medicine and cellular longevity Vol. 2016; no. 2016; pp. 1 - 6
• Main Authors: Geoffroy, Steve, Mamarbachi, Maya, Leblond, François, Nguyen, Albert, Thorin, Eric
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Age; Aging - drug effects; Aging - genetics; Aging - metabolism; Animals; Antioxidants; Catechin - pharmacology; Deoxyribonucleic acid; DNA; DNA Methylation; Endothelium; Enzymes; Epigenetic inheritance; Epigenetics; Femoral Artery - enzymology; Free radicals; Gene expression; Genes; Genomes; Hypotheses; Methylation; Mice; Nitric Oxide - genetics; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - biosynthesis; Nitric Oxide Synthase Type III - genetics; Oxidative stress; Physical Conditioning, Animal; Promoter Regions, Genetic; Studies; Superoxide; Superoxide Dismutase - biosynthesis; Superoxide Dismutase - genetics; Transcription, Genetic; Veins & arteries; Montreal Quebec Canada
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/8627384

We studied the age-dependent regulation of the expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD encoded by Sod2) through promoter methylation. C57Bl/6 mice were either (i) sedentary (SED), (ii) treated with the antioxidant catechin (CAT), or (iii) voluntarily exercised (EX) from weaning (1-month old; mo) to 9 mo. Then, all mice aged sedentarily and were untreated until 12 mo. Sod2 promoter methylation was similar in all groups in 9 mo but decreased (p<0.05) in 12 mo SED mice only, which was associated with an increased (p<0.05) transcriptional activity in vitro. At all ages, femoral artery endothelial function was maintained; this was due to an increased (p<0.05) contribution of eNOS-derived NO in 12 mo SED mice only. CAT and EX prevented these changes in age-related endothelial function. Thus, a ROS-dependent epigenetic positive regulation of Sod2 gene expression likely represents a defense mechanism prolonging eNOS function in aging mouse femoral arteries.