title: Free [NADH]/[NAD(+)] regulates sirtuin expression.
abstract: Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Fundacion Investigacion Hospital Clinico Universitario INCLIVA, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gambini
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Gomez-Cabrera
authors.forename: Consuelo
authors.initials: C
authors.lastname: Borras
authors.forename: Soraya L
authors.initials: SL
authors.lastname: Valles
authors.forename: Raul
authors.initials: R
authors.lastname: Lopez-Grueso
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Martinez-Bello
authors.forename: Daniel
authors.initials: D
authors.lastname: Herranz
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardo
authors.forename: Jesus A F
authors.initials: JA
authors.lastname: Tresguerres
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004331:Drosophila melanogaster; D000431:Ethanol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009243:NAD / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D019289:Pyruvic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D037761:Sirtuins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D009243:NAD; D019344:Lactic Acid; D000431:Ethanol; D019289:Pyruvic Acid; D037761:Sirtuins