TY - JOUR
T1 - Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle
AU - Radak, Zsolt
AU - Bori, Zoltan
AU - Koltai, Erika
AU - Fatouros, Ioannis G.
AU - Jamurtas, Athanasios Z.
AU - Douroudos, Ioannis I.
AU - Terzis, Gerasimos
AU - Nikolaidis, Michalis G.
AU - Chatzinikolaou, Athanasios
AU - Sovatzidis, Apostolos
AU - Kumagai, Shuzo
AU - Naito, Hisahi
AU - Boldogh, Istvan
N1 - Funding Information:
This work was supported by Hungarian Grants ETT 38388, TéT JAP13/02, JSPS (L-10566), and OTKA (K75702) awarded to Z. Radák and by AG 021830 (to I. Boldogh) from the U.S. NIH/NIA. We thank Mardelle Susman (Department of Microbiology and Immunology, UTMB) for careful editing of the manuscript.
PY - 2011/7/15
Y1 - 2011/7/15
N2 - 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.
AB - 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.
KW - 8-OxoG
KW - Acetylation
KW - Aging
KW - Antioxidants
KW - DNA damage/repair
KW - Exercise
KW - Free radicals
KW - OGG1
KW - Sirtuins
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U2 - 10.1016/j.freeradbiomed.2011.04.018
DO - 10.1016/j.freeradbiomed.2011.04.018
M3 - Article
C2 - 21569841
AN - SCOPUS:79959347376
SN - 0891-5849
VL - 51
SP - 417
EP - 423
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 2
ER -