Bo Hai, Wang Yi-He, Li Hai-Ying, Zhao Juan, Zhang Hong-Ying, Tong Chang-Qing
Department of Physiology and Pathophysiology, Medical College of Chinese People's Armed Police Force, Tianjin, China.
Sheng Li Xue Bao. 2008 Dec 25;60(6):767-76.
The physiological significance of skeletal muscle mitochondrial uncoupling protein 3 (UCP3) in hypoxia is elusive. In the current study, UCP3 mRNA and protein expressions were investigated along with mitochondrial respiratory function, reactive oxygen species (ROS) generation, as well as manganese superoxide dismutase (MnSOD) expression in rat skeletal muscle with or without endurance training after an acute and severe hypobaric hypoxia exposure for different time. Acute hypoxia induced a series of impairments in skeletal muscle mitochondrial bioenergetics. In untrained rats, UCP3 protein content increased by 60% above resting level at 4 h hypoxia, whereas MnSOD protein content and activity were unaltered. UCP3 upregulation increased mitochondrial uncoupling respiration thus reducing O2(.-) generation, but inevitably decreased ATP production. Training decreased acute hypoxia-induced upregulation of UCP3 protein (67% vs 42%) in rat skeletal muscle. ROS production in trained rats also showed a dramatic decrease at 2 h, 4 h and 6 h, respectively, compared with that in untrained rats. MnSOD protein contents and activities were significantly (50% and 34%) higher in trained than those in untrained rats. Training adaptation of MnSOD may enhance the mitochondrial tolerance to ROS production, and reduce UCP3 activation during severe hypoxia, thus maintaining the efficiency of oxidative phosphorylation. In trained rats, mitochondrial respiratory control (RCR) and P/O ratios were maintained relatively constant despite severe hypoxia, whereas in untrained rats RCR and P/O ratios were significantly decreased. These results indicate that (1) UCP3 mRNA and protein expression in rat skeletal muscle are upregulated during acute and severe hypobaric hypoxia, which may reduce the increased cross-membrane potential (Deltapsi) and thus ROS production; (2) Endurance training can blunt hypoxia-induced UCP3 upregulation, and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.
骨骼肌线粒体解偶联蛋白3（UCP3）在缺氧状态下的生理意义尚不明确。在本研究中，对急性严重低压缺氧暴露不同时间后，有无耐力训练的大鼠骨骼肌中UCP3的mRNA和蛋白表达、线粒体呼吸功能、活性氧（ROS）生成以及锰超氧化物歧化酶（MnSOD）表达进行了研究。急性缺氧导致骨骼肌线粒体生物能量学出现一系列损伤。在未经训练的大鼠中，缺氧4小时时UCP3蛋白含量比静息水平升高了60%，而MnSOD蛋白含量和活性未发生改变。UCP3上调增加了线粒体解偶联呼吸，从而减少了超氧阴离子（O2(.-)）生成，但不可避免地降低了ATP生成。训练减少了大鼠骨骼肌中急性缺氧诱导的UCP3蛋白上调（67%对42%）。与未经训练的大鼠相比，训练大鼠在2小时、4小时和6小时时的ROS生成也分别显著降低。训练大鼠的MnSOD蛋白含量和活性比未经训练的大鼠显著更高（分别高50%和34%）。MnSOD的训练适应性可能增强线粒体对ROS生成的耐受性，并在严重缺氧期间减少UCP3激活，从而维持氧化磷酸化的效率。在训练大鼠中，尽管存在严重缺氧，线粒体呼吸控制（RCR）和P/O比值仍保持相对恒定，而在未经训练的大鼠中，RCR和P/O比值显著降低。这些结果表明：（1）在急性严重低压缺氧期间，大鼠骨骼肌中UCP3的mRNA和蛋白表达上调，这可能降低增加的跨膜电位（Δψ），从而减少ROS生成；（2）耐力训练可减弱缺氧诱导的UCP3上调，并由于ROS清除增加而提高线粒体氧化磷酸化效率。
