Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest
Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest
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DOI：
10.1002/mus.20611
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发表时间：
2006-10-01
期刊：
影响因子：
3.4
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
--
作者：
Ogawa, Takayuki;Furochi, Harumi;Nikawa, Takeshi
在动物模型中，几种泛素连接酶在骨骼肌卸载引起的萎缩中起重要作用。在这项研究中，我们研究了蛋白质泛素化和泛素连接酶基因表达的股四头肌从健康志愿者卧床休息20天后，以澄清泛素依赖的蛋白水解在人体肌肉后卸载。卧床期间，股四头肌的厚度和横截面积分别显著下降4.6%和3.7%。泛素化的蛋白质在这些萎缩的人体肌肉中积累。实时逆转录-聚合酶链反应系统显示，卧床显著上调两个泛素连接酶基因，Cbl-b和atrogin-1的表达。我们还进行了DNA微阵列分析，以检查全面的基因表达在萎缩的肌肉。卧床主要抑制与控制骨骼肌基因表达相关的肌肉基因的表达。我们的研究结果表明，在人类中，Cbl-b-或atrogin-1介导的泛素化在卸载诱导的肌肉萎缩中起着重要作用，卸载应力可能会优先抑制骨骼肌中的转录反应。
In animal models, several ubiquitin ligases play an important role in skeletal muscle atrophy caused by unloading. In this study we examined protein ubiquitination and ubiquitin ligase gene expression in quadriceps femoris muscle from healthy volunteers after 20-day bedrest to clarify ubiquitin-dependent proteolysis in human muscles after unloading. During bedrest, thickness and cross-sectional area of the quadriceps femoris muscle decreased significantly by 4.6% and 3.7%, respectively. Ubiquitinated proteins accumulated in these atrophied human muscles. A real-time reverse transcription-polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl-b and atrogin-1. We also performed DNA microarray analysis to examine comprehensive gene expression in the atrophied muscle. Bedrest mainly suppressed the expression of muscle genes associated with control of gene expression in skeletal muscle. Our results suggest that, in humans, Cbl-b-or atrogin-1-mediated ubiquitination plays an important role in unloading-induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle.