Muscle and Aging Laboratory, Faculty of Kinesiology, University of Calgary, Calgary Alberta, Canada.
Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R544-53. doi: 10.1152/ajpregu.00250.2010. Epub 2010 Dec 9.
Artificial selection in rat has yielded high-capacity runners (HCR) and low-capacity runners (LCR) that differ in intrinsic (untrained) aerobic exercise ability and metabolic disease risk. To gain insight into how oxygen metabolism may have been affected by selection, we compared mitochondrial function, oxidative DNA damage (8-dihydroxy-guanosine; 8dOHG), and antioxidant enzyme activities in soleus muscle (Sol) and gastrocnemius muscle (Gas) of adult and aged LCR vs. HCR rats. In Sol of adult HCR rats, maximal ADP-stimulated respiration was 37% greater, whereas in Gas of adult HCR rats, there was a 23% greater complex IV-driven respiratory capacity and 54% greater leak as a fraction of electron transport capacity (suggesting looser mitochondrial coupling) vs. LCR rats. H(2)O(2) emission per gram of muscle was 24-26% greater for both muscles in adult HCR rats vs. LCR, although H(2)O(2) emission in Gas was 17% lower in HCR, after normalizing for citrate synthase activity (marker of mitochondrial content). Despite greater H(2)O(2) emission, 8dOHG levels were 62-78% lower in HCR rats due to 62-96% higher superoxide dismutase activity in both muscles and 47% higher catalase activity in Sol muscle in adult HCR rats, with no evidence for higher 8 oxoguanine glycosylase (OGG1; DNA repair enzyme) protein expression. We conclude that genetic segregation for high running capacity has generated a molecular network of cellular adaptations, facilitating a superior response to oxidative stress.
人工选择已产生了高能力奔跑者（HCR）和低能力奔跑者（LCR），它们在内在（未经训练）有氧运动能力和代谢疾病风险方面存在差异。为了深入了解氧气代谢如何受到选择的影响，我们比较了成年和老年 LCR 与 HCR 大鼠比目鱼肌（Sol）和腓肠肌（Gas）中的线粒体功能、氧化 DNA 损伤（8-二羟基鸟苷；8dOHG）和抗氧化酶活性。在成年 HCR 大鼠的 Sol 中，最大 ADP 刺激呼吸率增加了 37%，而在成年 HCR 大鼠的 Gas 中，复合物 IV 驱动的呼吸能力增加了 23%，电子传递能力的泄漏增加了 54%（表明线粒体偶联更松弛）与 LCR 大鼠相比。尽管 HCR 大鼠的 Gas 中 H2O2 排放降低了 17%（以柠檬酸合酶活性（线粒体含量的标志物）为基础），但成年 HCR 大鼠的 Sol 和 Gas 中的 H2O2 排放分别比 LCR 大鼠高 24-26%。由于两种肌肉中的超氧化物歧化酶活性分别增加了 62-96%，过氧化氢酶活性增加了 47%，Sol 肌肉中的 8 氧鸟嘌呤糖苷酶（OGG1；DNA 修复酶）蛋白表达没有增加，因此 HCR 大鼠中的 8dOHG 水平降低了 62-78%。我们的结论是，高奔跑能力的遗传分离产生了细胞适应的分子网络，为应对氧化应激提供了更好的响应。
