Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle

Zsolt Radak*, Zoltan Bori, Erika Koltai, Ioannis G. Fatouros, Athanasios Z. Jamurtas, Ioannis I. Douroudos, Gerasimos Terzis, Michalis G. Nikolaidis, Athanasios Chatzinikolaou, Apostolos Sovatzidis, Shuzo Kumagai, Hisahi Naito, Istvan Boldogh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

8-Oxo-7,8-dihydroguanine (8-oxoG) accumulates in the genome over time and is believed to contribute to the development of aging characteristics of skeletal muscle and various aging-related diseases. Here, we show a significantly increased level of intrahelical 8-oxoG and 8-oxoguanine-DNA glycosylase (OGG1) expression in aged human skeletal muscle compared to that of young individuals. In response to exercise, the 8-oxoG level was lastingly elevated in sedentary young and old subjects, but returned rapidly to preexercise levels in the DNA of physically active individuals independent of age. 8-OxoG levels in DNA were inversely correlated with the abundance of acetylated OGG1 (Ac-OGG1), but not with total OGG1, apurinic/apyrimidinic endonuclease 1 (APE1), or Ac-APE1. The actual Ac-OGG1 level was linked to exercise-induced oxidative stress, as shown by changes in lipid peroxide levels and expression of Cu,Zn-SOD, Mn-SOD, and SIRT3, as well as the balance between acetyltransferase p300/CBP and deacetylase SIRT1, but not SIRT6 expression. Together these data suggest that that acetylated form of OGG1, and not OGG1 itself, correlates inversely with the 8-oxoG level in the DNA of human skeletal muscle, and the Ac-OGG1 level is dependent on adaptive cellular responses to physical activity, but is age independent.

Original languageEnglish
Pages (from-to)417-423
Number of pages7
JournalFree Radical Biology and Medicine
Volume51
Issue number2
DOIs
Publication statusPublished - 2011 Jul 15
Externally publishedYes

Keywords

  • 8-OxoG
  • Acetylation
  • Aging
  • Antioxidants
  • DNA damage/repair
  • Exercise
  • Free radicals
  • OGG1
  • Sirtuins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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