Bo Hai, Li Ling, Duan Fu-Qiang, Zhu Jiang
Department of Military Training Medicines; Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury; Department of Pharmacology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, China; Department of Health, Tibet People's Armed Police Corps, Lasa 850000, China.
Sheng Li Xue Bao. 2014 Oct 25;66(5):597-604.
This study was undertaken to investigate the effect of exercise training on mitochondrial DNA (mtDNA) oxidative damage and 8-oxoguanine DNA glycosylase-1 (OGG1) expression in skeletal muscle of rats under continuous exposure to hypoxia. Male Sprague-Dawley rats were randomly divided into 4 groups (n = 8): normoxia control group (NC), normoxia training group (NT), hypoxia control group (HC), and hypoxia training group (HT). The hypoxia-treated animals were housed in normobaric hypoxic tent containing 11.3% oxygen for consecutive 4 weeks. The exercise-trained animals were exercised on a motor-driven rodent treadmill at a speed of 15 m/min, 5% grade for 60 min/day, 5 days per week for 4 weeks. The results showed that, compared with NC group, hypoxia attenuated complex I, II, IV and ATP synthase activities of the electron transport chain, and the level of mitochondrial membrane potential in HC group (P < 0.05 or P < 0.01). Moreover, hypoxia decreased mitochondrial OGG1, MnSOD, and GPx activities (P < 0.05 or P < 0.01), whereas elevated reactive oxygen species (ROS) generation and the level of 8-oxo-deoxyguanosine (8-oxodG) in mtDNA (P < 0.01). Furthermore, hypoxia attenuated muscle and mitochondrial [NAD⁺]/ [NADH] ratio, and SIRT3 protein expression (P < 0.05 or P < 0.01). Compared with HC group, exercise training in hypoxia elevated complex I, II, IV and ATP synthase activities, and the level of mitochondrial membrane potential in HT group (P < 0.05 or P < 0.01). Moreover, exercise training in hypoxia increased MnSOD and GPx activities and mitochondrial OGG1 level (P < 0.01), whereas decreased ROS generation and the level of 8-oxodG in mtDNA (P < 0.01). Furthermore, exercise training in hypoxia increased muscle and mitochondrial [NAD⁺]/[NADH] ratio, as well as SIRT3 protein expression (P < 0.05 or P < 0.01). These findings suggest that exercise training in hypoxia can decrease hypoxia-induced mtDNA oxidative damage in the skeletal muscle through up-regulating exercise-induced mitochondrial OGG1 and antioxidant enzymes. Exercise training in hypoxia may improve hypoxia tolerance in skeletal muscle mitochondria via elevating [NAD⁺]/[NADH] ratio and SIRT3 expression.
本研究旨在探讨运动训练对持续暴露于低氧环境下大鼠骨骼肌线粒体DNA（mtDNA）氧化损伤及8-氧代鸟嘌呤DNA糖基化酶-1（OGG1）表达的影响。雄性Sprague-Dawley大鼠随机分为4组（n = 8）：常氧对照组（NC）、常氧训练组（NT）、低氧对照组（HC）和低氧训练组（HT）。低氧处理的动物置于含11.3%氧气的常压低氧舱中连续饲养4周。运动训练的动物在电动啮齿动物跑步机上以15 m/min的速度、5%的坡度每天运动60 min，每周运动5天，共运动4周。结果显示，与NC组相比，低氧使HC组电子传递链复合物I、II、IV及ATP合酶活性降低，线粒体膜电位水平下降（P < 0.05或P < 0.01）。此外，低氧使线粒体OGG1、MnSOD和GPx活性降低（P < 0.05或P < 0.01），而mtDNA中活性氧（ROS）生成及8-氧代脱氧鸟苷（8-氧代dG）水平升高（P < 0.01）。此外，低氧使肌肉和线粒体的[NAD⁺]/[NADH]比值及SIRT3蛋白表达降低（P < 0.05或P < 0.01）。与HC组相比，低氧环境下的运动训练使HT组复合物I、II、IV及ATP合酶活性升高，线粒体膜电位水平升高（P < 0.05或P < 0.01）。此外，低氧环境下的运动训练使MnSOD和GPx活性及线粒体OGG1水平升高（P < 0.01），而mtDNA中ROS生成及8-氧代dG水平降低（P < 0.01）。此外，低氧环境下的运动训练使肌肉和线粒体的[NAD⁺]/[NADH]比值以及SIRT3蛋白表达升高（P < 0.05或P < 0.01）。这些研究结果表明，低氧环境下的运动训练可通过上调运动诱导的线粒体OGG1和抗氧化酶来减少低氧诱导的骨骼肌mtDNA氧化损伤。低氧环境下的运动训练可能通过提高[NAD⁺]/[NADH]比值和SIRT3表达来改善骨骼肌线粒体的低氧耐受性。
