title: Aerobic endurance capacity affects spatial memory and SIRT1 is a potent modulator of 8-oxoguanine repair.
abstract: Regular exercise promotes brain function via a wide range of adaptive responses, including the increased expression of antioxidant and oxidative DNA damage-repairing systems. Accumulation of oxidized DNA base lesions and strand breaks is etiologically linked to for example aging processes and age-associated diseases. Here we tested whether exercise training has an impact on brain function, extent of neurogenesis, and expression of 8-oxoguanine DNA glycosylase-1 (Ogg1) and SIRT1 (silent mating-type information regulation 2 homolog). To do so, we utilized strains of rats with low- and high-running capacity (LCR and HCR) and examined learning and memory, DNA synthesis, expression, and post-translational modification of Ogg1 hippocampal cells. Our results showed that rats with higher aerobic/running capacity had better spatial memory, and expressed less Ogg1, when compared to LCR rats. Furthermore, exercise increased SIRT1 expression and decreased acetylated Ogg1 (AcOgg1) levels, a post-translational modification important for efficient repair of 8-oxo-7,8-dihydroguanine (8-oxoG). Our data on cell cultures revealed that nicotinamide, a SIRT1-specific inhibitor, caused the greatest increase in the acetylation of Ogg1, a finding further supported by our other observations that silencing SIRT1 also markedly increased the levels of AcOgg1. These findings imply that high-running capacity is associated with increased hippocampal function, and SIRT1 level/activity and inversely correlates with AcOgg1 levels and thereby the repair of genomic 8-oxoG.
authors: Research Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest H-1123, Hungary; Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
authors: L
authors: L
authors: Sarga
authors: N
authors: N
authors: Hart
authors: L G
authors: LG
authors: Koch
authors: S L
authors: SL
authors: Britton
authors: G
authors: G
authors: Hajas
authors: I
authors: I
authors: Boldogh
authors: X
authors: X
authors: Ba
authors: Z
authors: Z
authors: Radak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045647:DNA Glycosylases / Q000096:biosynthesis*; D004260:DNA Repair / Q000502:physiology; D055785:Gene Knockdown Techniques; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D034741:RNA, Small Interfering; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000096:biosynthesis*; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: 4-dinitrophenylhydrazine; 5-bromo-2′-deoxyuridine; 8-oxo-7,8-dihydroguanine; 8-oxoG; 8-oxoguanine DNA glycosylase-1; AP; APE1; Ac; AcOgg1; BER; BrdU; DNA repair; DNPH; ERK; GAD; HCR; HDAC; HRP; LCR; NAD; NAM; NGF; OGG1; Ogg1; TBS; TBS-T; TSA; TrHCR; TrLCR; abasic; acetylated; acetylated 8-oxoguanine DNA glycosylase-1; apurinic apyrimidinic endonuclease1; base excision repair; exercise; extracellular signal-regulated kinase; glutamic acid decarboxylase; high-running capacity; hippocampus; histone deacetylase; horseradish peroxidase; low-running capacity; nerve growth factor; nicotinamide; nicotinamide adenine dinucleotide; single-strand breaks; ssbs; trained HCR; trained LCR; trichostatin A; tris-buffered saline; tris-buffered saline containing 0.1% Tween
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