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

Research output: Contribution to journalArticle

66 Scopus citations

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 (US)
Pages (from-to)417-423
Number of pages7
JournalFree Radical Biology and Medicine
Volume51
Issue number2
DOIs
StatePublished - Jul 15 2011

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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    Radak, Z., Bori, Z., Koltai, E., Fatouros, I. G., Jamurtas, A. Z., Douroudos, I. I., Terzis, G., Nikolaidis, M. G., Chatzinikolaou, A., Sovatzidis, A., Kumagai, S., Naito, H., & Boldogh, I. (2011). Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle. Free Radical Biology and Medicine, 51(2), 417-423. https://doi.org/10.1016/j.freeradbiomed.2011.04.018