title: Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3T 1J4; Research Centre, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada H1T 1C8.
authors.forename: Albert
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3T 1J4; Research Centre, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada H1T 1C8; Novartis Pharmaceuticals Canada Inc., Dorval, QC, Canada H9S 1A9.
authors.forename: François
authors.initials: F
authors.lastname: Leblond
authors.affiliation: Research Centre, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada H1T 1C8.
authors.forename: Maya
authors.initials: M
authors.lastname: Mamarbachi
authors.affiliation: Research Centre, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada H1T 1C8.
authors.forename: Steve
authors.initials: S
authors.lastname: Geoffroy
authors.affiliation: Research Centre, Montreal Heart Institute, 5000 Belanger Street, Montreal, QC, Canada H1T 1C8; Department of Surgery, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3T 1J4.
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000494:pharmacology; D019175:DNA Methylation; D005263:Femoral Artery / Q000201:enzymology*; D051379:Mice; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D010805:Physical Conditioning, Animal; D011401:Promoter Regions, Genetic; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D000099156:Superoxide Dismutase 2
chemical_list: D002392:Catechin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C496315:Nos3 protein, mouse