Activation of the hypoxia-inducible factor pathway induced by prolyl hydroxylase domain 2 deficiency enhances the effect of running training in mice.
Activation of the hypoxia-inducible factor pathway induced by prolyl hydroxylase domain 2 deficiency enhances the effect of running training in mice.
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DOI：
10.1111/apha.12751
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Nagatomi R
中科院分区：
文献类型：
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作者：
Nunomiya A;Shin J;Kitajima Y;Dan T;Miyata T;Nagatomi R
由缺氧诱导因子（HIF）介导的缺氧反应似乎有助于耐力训练的益处。为了验证HIF激活对跑步训练的直接贡献，而不暴露于大气缺氧，我们使用脯氨酰羟化酶结构域2（PHD 2）条件性敲除小鼠（cKO），其表现出HIF激活独立于氧浓度，我们检查了他们的最大运动能力之前和之后4周的跑步机运动训练。 将Phd 2 f/f小鼠（n = 26）和Phd 2 cKO小鼠（n = 24）随机分为两组，训练组和未训练组，并在4周跑步机训练方案前后进行最大跑步测试。脯氨酰羟化酶结构域2缺陷导致HIF-α蛋白积聚。Phd 2 cKO小鼠表现出红细胞压积值和血红蛋白浓度的显著增加，以及骨骼肌中毛细血管数量的增加。4周的训练引起骨骼肌的毛细血管与纤维（C/F）比率和琥珀酰脱氢酶活性增加。重要的是，训练的Phd 2 cKO小鼠在跑步时间上显示出比训练的对照小鼠显著更大的改善（P < 0.05）。总的来说，这些数据表明，训练和HIF通路的激活相结合对于最大化跑步训练的效果是重要的。我们的结论是，PHD 2缺乏诱导的HIF通路的激活增强了跑步训练的效果。
Hypoxic response mediated by hypoxia‐inducible factor (HIF) seems to contribute to the benefit of endurance training. To verify the direct contribution of HIF activation to running training without exposure to atmospheric hypoxia, we used prolyl hydroxylase domain 2 (PHD2) conditional knockout mice (cKO), which exhibit HIF activation independent of oxygen concentration, and we examined their maximal exercise capacity before and after 4 weeks of treadmill exercise training. Phd2 f/f mice (n = 26) and Phd2 cKO mice (n = 24) were randomly divided into two groups, trained and untrained, and were subjected to maximal running test before and after a 4‐week treadmill‐training regimen. Prolyl hydroxylase domain 2 deficiency resulted in HIF‐α protein accumulation. Phd2 cKO mice exhibited marked increases in haematocrit values and haemoglobin concentrations, as well as an increase in the capillary number in the skeletal muscle. The 4‐week training elicited an increase in the capillary‐to‐fibre (C/F) ratio and succinyl dehydrogenase activity of the skeletal muscle. Importantly, trained Phd2 cKO mice showed a significantly greater improvement in running time than trained control mice (P < 0.05). Collectively, these data suggest that the combination of training and the activation of the HIF pathway are important for maximizing the effect of running training. We conclude that the activation of the HIF pathway induced by PHD2 deficiency enhances the effect of running training.