Radak Zsolt, Kumagai Shuzo, Nakamoto Hideko, Goto Sataro
Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest, Hungary.
J Appl Physiol (1985). 2007 Apr;102(4):1696-701. doi: 10.1152/japplphysiol.01051.2006. Epub 2007 Jan 4.
Oxoguanine DNA glycosylase (OGG1) and uracil DNA glycosylase (UDG) are two of the most important repair enzymes that are involved in the base excision repair processes to eliminate oxidative damage from mammalian DNA, which accumulates with aging. Red and white skeletal muscle fibers have very different antioxidant enzyme activities and resistance to oxidative stress. In this paper, we demonstrate that the activity of OGG1 is significantly higher in the red type of skeletal muscle compared with white fibers from old rats. Exercise training resulted in increased OGG1 activity in the nuclei of red fibers and decreased activity in nuclei of white fibers and in the mitochondria of both red and white fibers. The activities of UDG were similar in both red and white muscle fibers. Exercise training appears to increase the activity of UDG in the nuclei and mitochondria. However, exercise training affects the activity of OGG1 in nuclei and mitochondria differently, suggesting different regulation of the enzymes. In contrast, UDG showed similar activities in nuclei and mitochondrial extracts of exercise-trained animals. These data provide evidence for differential regulation of UDG and OGG1 in maintaining fidelity of DNA in oxidatively stressed cells.
氧代鸟嘌呤DNA糖基化酶(OGG1)和尿嘧啶DNA糖基化酶(UDG)是参与碱基切除修复过程以消除哺乳动物DNA氧化损伤的两种最重要的修复酶,这种氧化损伤会随着衰老而积累。红色和白色骨骼肌纤维具有非常不同的抗氧化酶活性和对氧化应激的抵抗力。在本文中,我们证明,与老年大鼠的白色纤维相比,OGG1在红色类型的骨骼肌中的活性显著更高。运动训练导致红色纤维细胞核中OGG1活性增加,而白色纤维细胞核以及红色和白色纤维线粒体中的活性降低。UDG在红色和白色肌纤维中的活性相似。运动训练似乎会增加细胞核和线粒体中UDG的活性。然而,运动训练对细胞核和线粒体中OGG1活性的影响不同,这表明这两种酶受到不同的调节。相比之下,在运动训练动物的细胞核和线粒体提取物中,UDG显示出相似的活性。这些数据为在氧化应激细胞中维持DNA保真度时UDG和OGG1的差异调节提供了证据。