Hypoxia differentially regulates muscle oxidative fiber type and metabolism in a HIF-1α-dependent manner.
Hypoxia differentially regulates muscle oxidative fiber type and metabolism in a HIF-1α-dependent manner.
复制标题
缺氧以 HIF-1α 依赖性方式差异调节肌肉氧化纤维类型和代谢。
DOI：
10.1016/j.cellsig.2014.04.016
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发表时间：
2014
影响因子：
4.8
通讯作者：
H. Gosker
中科院分区：
文献类型：
--
作者：
I. Slot;A. Schols;B. Vosse;M. Kelders;H. Gosker
骨骼肌氧化纤维类型和线粒体能力的丧失是慢性阻塞性肺疾病和慢性心力衰竭的标志。在活体人和动物研究的基础上，组织缺氧被认为是决定因素，但缺氧对肌肉氧化表型的直接影响仍有待确定。因此，我们确定了低氧对体外培养的肌肉细胞的影响，包括线粒体成分、肌球蛋白异构体(反映慢氧化和快糖酵解纤维)的基因和蛋白表达水平，以及调节PPAR/PGC-1α通路的参与。我们发现低氧通过抑制PPAR/PGC-1α途径和通过HIF-1α抑制线粒体成分的表达。然而，与我们的假设相反，低氧刺激了缓慢氧化的I型肌球蛋白通过HIF-1α的表达。总之，这项研究表明，低氧以HIF-1α依赖的方式不同地调节肌肉氧化表型的收缩和代谢成分。
Loss of skeletal muscle oxidative fiber types and mitochondrial capacity is a hallmark of chronic obstructive pulmonary disease and chronic heart failure. Based onin vivohuman and animal studies, tissue hypoxia has been hypothesized as determinant, but the direct effect of hypoxia on muscle oxidative phenotype remains to be established. Hence, we determined the effect of hypoxia onin vitrocultured muscle cells, including gene and protein expression levels of mitochondrial components, myosin isoforms (reflecting slow-oxidativeversusfast-glycolytic fibers), and the involvement of the regulatory PPAR/PGC-1α pathway. We found that hypoxia inhibits the PPAR/PGC-1α pathway and the expression of mitochondrial components through HIF-1α. However, in contrast to our hypothesis, hypoxia stimulated the expression of slow-oxidative type I myosinviaHIF-1α. Collectively, this study shows that hypoxia differentially regulates contractile and metabolic components of muscle oxidative phenotype in a HIF-1α-dependent manner.
影响因子：
29
作者：
Kim, JW;Tchernyshyov, I;Dang, CV
通讯作者：
Dang, CV
影响因子：
29
作者：
Papandreou, I;Cairns, RA;Denko, NC
通讯作者：
Denko, NC
影响因子：
29
作者：
Arany, Z;He, HM;Spiegelman, BM
通讯作者：
Spiegelman, BM