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

Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle.
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DOI:
10.1016/j.freeradbiomed.2011.04.018
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发表时间:
2011-07-15
影响因子:
7.4
通讯作者:
Boldogh, Istvan
Boldogh, Istvan
中科院分区:
医学1区
文献类型:
--
作者:
Radak, Zsolt;Bori, Zoltan;Koltai, Erika;Fatouros, Ioannis G.;Jamurtas, Athanasios Z.;Douroudos, Ioannis I.;Terzis, Gerasimos;Nikolaidis, Michalis G.;Chatzinikolaou, Athanasios;Sovatzidis, Apostolos;Kumagai, Shuzo;Naito, Hisahi;Boldogh, Istvan

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8-Oxo-7,8 二氢鸟嘌呤 (8-oxoG) 随着时间的推移在基因组中积累,被认为有助于骨骼肌衰老特征和各种衰老相关疾病的发展。在这里,我们发现与年轻个体相比,老年人骨骼肌中螺旋内 8-oxoG 和 8-oxoguanine DNA 糖基化酶 (OGG1) 的表达水平显着增加。作为对运动的反应,久坐的年轻人和老年受试者的 8-oxoG 水平持续升高,但无论年龄如何,身体活跃的个体 DNA 中的 8-oxoG 水平都会迅速恢复到运动前的水平。 DNA 中的 8-OxoG 水平与乙酰化 OGG1 (Ac-OGG1) 的丰度呈负相关,但与总 OGG1、脱嘌呤/脱嘧啶核酸内切酶 (AP)-1 或 Ac-APE1 不相关。实际的 Ac-OGG1 水平与运动引起的氧化应激有关,如脂质过氧化物水平和 Cu、Zn-SOD、Mn-SOD 和 SIRT3 表达的变化以及乙酰转移酶 p300/CBP 和脱乙酰酶 SIRT1 之间的平衡(但不包括 SIRT6 表达)所示。这些数据一起表明OGG1的乙酰化形式而不是OGG1本身与人骨骼肌DNA中的8-oxoG水平成反比,并且Ac-OGG1水平依赖于对身体活动的适应性细胞反应,但与年龄无关。
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 found to be lastingly elevated in sedentary young and old subjects, but returned rapidly to pre-exercise 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 (AP)-1 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 acetyl transferase p300/CBP and the deacetylase SIRT1, but not SIRT6 expression. Together these data suggest that that acetylated form of OGG1, and not OGGl 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.
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