Muscle hypertrophy is associated with increases in proteasome activity that is independent of MuRF1 and MAFbx expression.
Muscle hypertrophy is associated with increases in proteasome activity that is independent of MuRF1 and MAFbx expression.
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DOI：
10.3389/fphys.2014.00069
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发表时间：
2014
影响因子：
4
通讯作者：
Bodine SC
中科院分区：
文献类型：
--
作者：
Baehr LM;Tunzi M;Bodine SC
骨骼肌质量的调节取决于蛋白质合成和降解之间的平衡。蛋白质降解，特别是泛素蛋白酶体系统，以及E3泛素连接酶MuRF1和MAFbx/atrogin-1的表达增加，在对生长刺激的肌肉大小调节中的作用尚不清楚。因此，本研究的目的是使用功能过载（FO）模型测量小鼠在14天的慢性负荷期间的蛋白酶体活性和蛋白质合成。此外，通过测量MuRF1或MAFbx零缺失（KO）小鼠对FO的肌肉生长反应，研究了MuRF1和MAFbx表达在调节肌肉肥大中的重要性。在野生型（WT）小鼠中，肌肉质量的增加与第7天和第14天蛋白质合成的显著增加（2倍）相关。有趣的是，WT小鼠的蛋白酶体活性在1天后显著增加，并继续增加，在FO后7天达到峰值。蛋白酶体活性的增加与叉头转录因子FOXO1和FOXO3a的表达增加相关，在MuRF1和MAFbx增加并恢复到基线后，FOXO1和FOXO3a的表达也增加。与WT小鼠一样，在14天后，MuRF1和MAFbx KO小鼠的肥大与蛋白酶体活性的显著增加有关。FO后，WT和MuRF1 KO小鼠的足底重量增加相似，但雌性MAFbx KO小鼠的肌肉生长明显减少。总的来说，这些结果表明肌肉肥大与蛋白质合成和降解的增加有关。此外，在负荷增加后，增加蛋白酶体活性并不需要MuRF1或MAFbx的表达，然而，在负荷增加时肌肉的正常生长/重塑可能需要MAFbx的表达。
The regulation of skeletal muscle mass depends on the balance between protein synthesis and degradation. The role of protein degradation and in particular, the ubiquitin proteasome system, and increased expression of the E3 ubiquitin ligases, MuRF1 and MAFbx/atrogin-1, in the regulation of muscle size in response to growth stimuli is unclear. Thus, the aim of this study was to measure both proteasome activity and protein synthesis in mice over a 14-day period of chronic loading using the functional overload (FO) model. Further, the importance of MuRF1 and MAFbx expression in regulating muscle hypertrophy was examined by measuring muscle growth in response to FO in mice with a null deletion (KO) of either MuRF1 or MAFbx. In wild type (WT) mice, the increase in muscle mass correlated with significant increases (2-fold) in protein synthesis at 7 and 14 days. Interestingly, proteasome activity significantly increased in WT mice after one day, and continued to increase, peaking at 7 days following FO. The increase in proteasome activity was correlated with increases in the expression of the Forkhead transcription factors, FOXO1 and FOXO3a, which increased after both MuRF1 and MAFbx increased and returned to baseline. As in WT mice, hypertrophy in the MuRF1 and MAFbx KO mice was associated with significant increases in proteasome activity after 14 days of FO. The increase in plantaris mass was similar between the WT and MuRF1 KO mice following FO, however, muscle growth was significantly reduced in female MAFbx KO mice. Collectively, these results indicate that muscle hypertrophy is associated with increases in both protein synthesis and degradation. Further, MuRF1 or MAFbx expression is not required to increase proteasome activity following increased loading, however, MAFbx expression may be required for proper growth/remodeling of muscle in response to increase loading.
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影响因子：
11.4
作者：
Lagirand-Cantaloube, Julie;Offner, Nicolas;Leibovitch, Serge A.
通讯作者：
Leibovitch, Serge A.
影响因子：
5.5
作者：
Goodman, Craig A.;Frey, John W.;Hornberger, Troy A.
通讯作者：
Hornberger, Troy A.
DOI：
10.1083/jcb.200901052
发表时间：
2009-06-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cohen S;Brault JJ;Gygi SP;Glass DJ;Valenzuela DM;Gartner C;Latres E;Goldberg AL
通讯作者：
Goldberg AL
DOI：
10.1016/j.biocel.2008.04.010
发表时间：
2008-01-01
影响因子：
4
作者：
Kubica, Neil;Crispino, Jamie L.;Jefferson, Leonard S.
通讯作者：
Jefferson, Leonard S.
影响因子：
--
作者：
Lokireddy, Sudarsanareddy;McFarlane, Craig;Kambadur, Ravi
通讯作者：
Kambadur, Ravi