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首页> 外文期刊>Journal of Molecular Biology >Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice.
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Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice.

机译：MuRF1的诱导对于TNF-α诱导的小鼠肌肉功能丧失至关重要。

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BACKGROUND: Humoral circulating inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) can impair skeletal muscle contractility. Furthermore, TNF-alpha expression correlates with elevated levels of atrogin-like muscle-specific ubiquitin E3 ligases, which are presumed to mediate muscle protein breakdown and atrophy. However, the casual relationships between MuRF1 and TNF-alpha and their relative contributions to muscle function impairment are not known. METHODS: TNF-alpha or saline was injected into either C57Bl6 or MuRF1(-/-) mice. After 16-24 h, the expression of MuRF1 in skeletal muscle was quantified by quantitative reverse transcription-PCR and Western blot analysis. Muscle function was measured in an organ bath. To obtain a broader overview on potential alterations, two-dimensional gel electrophoresis was performed. RESULTS: Wild-type animals injected with TNF-alpha had higher MuRF1 mRNA expression (saline versus TNF-alpha: 56.6+/-12.1 versus 133.6+/-30.3 arbitrary units; p<0.05) and protein expression (saline versus TNF-alpha: 0.38+/-0.11 versus 1.07+/-0.25 arbitrary units; p<0.05) as compared to saline-injected littermates. Furthermore, TNF-alpha reduced force development at 150 Hz by 25% in C57Bl6 animals (saline versus TNF-alpha: 2412+/-120 versus 1799+/-114 g/cm(2); p<0.05), but not in MuRF1(-/-) mice (saline versus TNF-alpha: 2424+/-198 versus 2431+/-180 g/cm(2); p=NS). Proteome analysis revealed a significant down-regulation of fast skeletal muscle troponin T in wild-type animals treated with TNF-alpha as compared to MuRF1(-/-) mice that received TNF-alpha. CONCLUSION: The results of this study demonstrate for the first time that TNF-alpha-induced reduction in skeletal muscle force development depends on the induction of the atrophy-related E3 ubiquitin ligase MuRF1. A link for the reduction in muscle force may be the TNF-alpha/MuRF1-mediated down-regulation of fast skeletal muscle troponin T.
机译：背景：体液循环炎症细胞因子，例如肿瘤坏死因子α（TNF-alpha）可以损害骨骼肌的收缩力。此外，TNF-α的表达与Atrogin样肌肉特异性泛素E3连接酶水平升高有关，后者可能介导肌肉蛋白的降解和萎缩。但是，MuRF1和TNF-α之间的随意关系及其对肌肉功能受损的相对作用尚不清楚。方法：将TNF-α或盐水注射入C57B16或MuRF1（-/-）小鼠。 16-24小时后，通过定量逆转录PCR和蛋白质印迹分析定量MuRF1在骨骼肌中的表达。在器官浴中测量肌肉功能。为了获得有关电位改变的更广泛的概述，进行了二维凝胶电泳。结果：注射TNF-α的野生型动物具有更高的MuRF1 mRNA表达（盐对TNF-α：56.6 +/- 12.1对133.6 +/- 30.3任意单位; p <0.05）和蛋白质表达（盐对TNF-α） ：与注射盐水的同窝仔猪相比，为：0.38 +/- 0.11与1.07 +/- 0.25任意单位; p <0.05）。此外，TNF-α在C57B16动物中在150 Hz下将力发展降低了25％（盐水对TNF-α：2412 +/- 120对1799 +/- 114 g / cm（2）; p <0.05），但在MuRF1（-/-）小鼠（盐对TNF-α：2424 +/- 198对2431 +/- 180 g / cm（2）; p = NS）。蛋白质组学分析显示，与接受TNF-α的MuRF1（-/-）小鼠相比，用TNF-α治疗的野生型动物中快速骨骼肌肌钙蛋白T明显下调。结论：本研究结果首次证明TNF-α诱导的骨骼肌力量发展的减少取决于与萎缩相关的E3泛素连接酶MuRF1的诱导。减少肌肉力量的一个环节可能是TNF-α/ MuRF1介导的快速骨骼肌肌钙蛋白T的下调。

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