Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation
Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation
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DOI：
10.1096/fj.12-204495
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发表时间：
2012-07-01
期刊：
影响因子：
4.8
通讯作者：
Bodine, Sue C.
中科院分区：
文献类型：
--
作者：
Gomes, Aldrin V.;Waddell, Dave S.;Bodine, Sue C.
删除肌肉环指1（MuRF 1），E3泛素连接酶，导致肌肉质量的保留后去神经支配。本研究的目的是测试的假设，肌肉保留在小鼠与MuRF 1的缺失是由于选择性抑制泛素蛋白酶体系统。20 S和26 S蛋白酶体，钙蛋白酶和组织蛋白酶L的活性，测定野生型（WT）和MuRF 1基因敲除（KO）小鼠的小腿三头肌在3和14天后去神经支配。此外，在WT和KO肌肉中测量蛋白质合成率分数和差异基因表达。主要的发现是，20 S和26 S蛋白酶体的活性显着升高（1.5至2.5倍）后，14天的WT和KO小鼠去神经相对于对照组，但有趣的是，20 S和26 S蛋白酶体的活性显着高于KO比WT小鼠。此外，MAFbx的mRNA表达在KO小鼠去神经支配14天后升高，但WT小鼠没有。这些数据挑战了MuRF 1仅控制收缩蛋白降解的传统教条，并表明MuRF 1在泛素蛋白酶体系统和蛋白质周转的全球控制中发挥作用。Gomes，A.五、Waddell，D.美国，Siu河，Stein，M.，杜威，S.，Furlow，J.D.，Bodine，S. C.去神经支配后RING指1缺失小鼠肌肉中蛋白酶体活性的上调。FASEB J.26，2986-2999（2012）。www.fasebj.org
Deletion of muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, leads to sparing of muscle mass following denervation. The purpose of this study was to test the hypothesis that muscle sparing in mice with a deletion of MuRF1 is due to the selective inhibition of the ubiquitin proteasome system. Activities of the 20S and 26S proteasomes, calpain and cathepsin L, were measured in the triceps surae muscles of wild-type (WT) and MuRF1-knockout (KO) mice at 3 and 14 d following denervation. In addition, fractional protein synthesis rates and differential gene expression were measured in WT and KO muscle. The major finding was that 20S and 26S proteasome activities were significantly elevated (1.5- to 2.5-fold) after 14 d of denervation in both WT and KO mice relative to control, but interestingly, the activities of both the 20S and 26S proteasome were significantly higher in KO than WT mice. Further, mRNA expression of MAFbx was elevated after 14 d of denervation in KO, but not WT, mice. These data challenge the conventional dogma that MuRF1 is controlling the degradation of only contractile proteins and suggest a role for MuRF1 in the global control of the ubiquitin proteasome system and protein turnover.-Gomes, A. V., Waddell, D. S., Siu, R., Stein, M., Dewey, S., Furlow, J. D., Bodine, S. C. Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation. FASEB J. 26, 2986-2999 (2012). www.fasebj.org