Research Institute of Sport Science, Semmelweis University, Budapest H-1123, Hungary.
Free Radic Biol Med. 2011 Jul 15;51(2):417-23. doi: 10.1016/j.freeradbiomed.2011.04.018. Epub 2011 Apr 15.
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.
8-氧代-7,8-二氢鸟嘌呤（8-氧代 G）随着时间的推移在基因组中积累，被认为导致骨骼肌衰老特征和各种与衰老相关疾病的发展。在这里，我们显示与年轻人相比，衰老的人类骨骼肌中存在明显更高水平的螺旋内 8-氧代 G 和 8-氧代鸟嘌呤-DNA 糖基化酶（OGG1）表达。响应运动，久坐的年轻和老年受试者的 8-氧代 G 水平持久升高，但在活跃的个体中，无论年龄如何，8-氧代 G 水平都迅速恢复到运动前水平。DNA 中的 8-氧代 G 水平与乙酰化 OGG1（Ac-OGG1）的丰度呈反比，但与总 OGG1、脱嘌呤/脱嘧啶内切酶 1（APE1）或 Ac-APE1 无关。如脂质过氧化物水平和 Cu、Zn-SOD、Mn-SOD 和 SIRT3 的表达变化以及乙酰转移酶 p300/CBP 和去乙酰化酶 SIRT1 之间的平衡所表明的那样，实际的 Ac-OGG1 水平与运动引起的氧化应激有关，但与 SIRT6 表达无关。这些数据表明，乙酰化形式的 OGG1，而不是 OGG1 本身，与人类骨骼肌 DNA 中的 8-氧代 G 水平呈反比，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。
