Department of Health Science, Wuhan Institute of Physical Education, Luoyu Road No. 461, Wuhan City, Hubei Province, China.
Life Sci. 2011 Jul 4;89(1-2):44-9. doi: 10.1016/j.lfs.2011.04.018. Epub 2011 May 18.
MuRF1 E3 ubiquitin ligase has been identified as a mediator of skeletal muscle wasting in various skeletal muscle atrophy models, and its expression is upregulated by oxidative stress. Exercise training could decrease oxidative stress and restore the atrophied skeletal muscle. Here, our aim was to investigate whether exercise training has any effect on MuRF1 expression in rats with diabetes.
Rats with streptozotocin-induced diabetes were subjected to exercise training, after which oxidative stress was determined, and MuRF1 expression was analyzed by immunohistochemistry, real-time RT-PCR and Western blot analysis. In addition, we analyzed C2C12 myotubes in an in vitro model to examine the effects of oxidative stress on the protein levels of MuRF1 and myosin heavy chain (MHC).
While oxidative stress and MuRF1 expression were increased in rats with diabetes, exercise training diminished the skeletal muscle wasting in diabetic rats by decreasing oxidative stress and inhibiting MuRF1 expression at both the mRNA and protein levels. In addition, oxidative stress-induced MuRF1 upregulation promoted proteasome dependent degradation of the myosin heavy chain (MHC) in C2C12 myotubes.
Our study provides the first evidence that the beneficial anti-atrophy effects of exercise training on diabetes might be mediated by inhibiting oxidative stress-induced MuRF1 upregulation and preventing MuRF1-mediated degradation of MHC.
肌萎缩蛋白 1（MuRF1）E3 泛素连接酶已被确定为多种骨骼肌萎缩模型中骨骼肌萎缩的介质，其表达可被氧化应激上调。运动训练可减少氧化应激并恢复萎缩的骨骼肌。在这里，我们的目的是研究运动训练是否对糖尿病大鼠的 MuRF1 表达有影响。
链脲佐菌素诱导糖尿病大鼠进行运动训练，测定氧化应激，通过免疫组织化学、实时 RT-PCR 和 Western blot 分析检测 MuRF1 表达。此外，我们还在体外模型中分析 C2C12 肌管，以研究氧化应激对 MuRF1 和肌球蛋白重链（MHC）蛋白水平的影响。
虽然糖尿病大鼠的氧化应激和 MuRF1 表达增加，但运动训练通过降低氧化应激和抑制 MuRF1 在 mRNA 和蛋白水平的表达，减轻了糖尿病大鼠的骨骼肌萎缩。此外，氧化应激诱导的 MuRF1 上调促进了 C2C12 肌管中肌球蛋白重链（MHC）的蛋白酶体依赖性降解。
我们的研究首次提供了证据表明，运动训练对糖尿病的有益抗萎缩作用可能是通过抑制氧化应激诱导的 MuRF1 上调和防止 MuRF1 介导的 MHC 降解来介导的。
