Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona 08028, Spain.
Muscle Nerve. 2011 Feb;43(2):268-73. doi: 10.1002/mus.21852.
Proteolysis in skeletal muscle is mainly carried out by the activity of the ubiquitin-dependent proteolytic system. For the study of protein degradation through the ubiquitin-proteasome pathway, we used a model of hyperthermia in murine myotubes. In C2C12 cells, hyperthermia (41°C) induced a significant increase in both the rate of protein synthesis (18%) and degradation (51%). Interestingly, the addition of the β(2) -adrenoceptor agonist formoterol resulted in a significant decrease in protein degradation (21%) without affecting protein synthesis. The decrease in proteolytic rate was associated with decreases in gene expression of the different components of the ubiquitin-dependent proteolytic system. The effects of the β(2) -agonist on protein degradation were dependent exclusively on cAMP formation, because inhibition of adenylyl cyclase completely abolished the effects of formoterol on protein degradation. It can be concluded that hyperthermia is a suitable model for studying the anti-proteolytic potential of drugs used in the treatment of muscle wasting.
骨骼肌中的蛋白水解主要通过泛素依赖的蛋白水解系统的活性来完成。为了研究通过泛素-蛋白酶体途径进行的蛋白降解，我们使用了鼠肌管高热模型。在 C2C12 细胞中，高热（41°C）诱导蛋白合成（18%）和降解（51%）的显著增加。有趣的是，β(2)-肾上腺素受体激动剂福莫特罗的添加导致蛋白降解的显著减少（21%），而不影响蛋白合成。蛋白水解率的降低与泛素依赖的蛋白水解系统的不同组成部分的基因表达降低有关。β(2)-激动剂对蛋白降解的影响完全依赖于 cAMP 的形成，因为腺嘌呤核苷环化酶的抑制完全消除了福莫特罗对蛋白降解的影响。可以得出结论，高热是研究用于治疗肌肉减少症的药物的抗蛋白水解潜力的合适模型。
