Berthon P, Duguez S, Favier F B, Amirouche A, Feasson L, Vico L, Denis C, Freyssenet D
Laboratoire de Physiologie et de Biomécanique de l'Exercice Musculaire, Université Rennes 2, Rennes F-35000, France.
Pflugers Arch. 2007 Jul;454(4):625-33. doi: 10.1007/s00424-007-0230-6. Epub 2007 Mar 3.
In the present study, we determined the impact of 5 and 10 days of muscle deconditioning induced by hindlimb suspension (HS) on the ubiquitin-proteasome system of protein degradation and caspase enzyme activities in rat soleus muscles. A second goal was to determine whether activities of matrix metalloproteinase-2/9 (MMP-2/9) and urokinase-type/tissue-type plasminogen activator (PAs) were responsive to HS. As expected, HS led to a pronounced atrophy of soleus muscle. Level of ubiquitinated proteins, chymotrypsin-like activity of 20S proteasome, and Bcl-2-associated gene product-1 protein level were all transitory increased in response to 5 days of HS. These changes may thus potentially account for the decrease in muscle mass observed in response to 5 days of HS. Caspase-3 activity was significantly increased throughout the experimental period, whereas activities of caspase-6, another effector caspase, and caspase-9, the mitochondrial-dependent activator of both caspase-3 and -6, were only increased in response to 10 days of HS. This suggests that caspase-3 may be regulated through mitochondrial-independent and mitochondrial-dependent mechanisms in response to HS. Finally, MMP-2/9 activities remained unchanged, whereas PAs activities were increased after 5 days of HS. Overall, these data suggest that time-dependent regulation of intracellular and extracellular proteinases are important in setting the new phenotype of rat soleus muscle in response to HS.
在本研究中，我们确定了后肢悬吊（HS）诱导的5天和10天肌肉去适应对大鼠比目鱼肌中蛋白质降解的泛素-蛋白酶体系统和半胱天冬酶活性的影响。第二个目标是确定基质金属蛋白酶-2/9（MMP-2/9）和尿激酶型/组织型纤溶酶原激活剂（PA）的活性是否对HS有反应。正如预期的那样，HS导致比目鱼肌明显萎缩。泛素化蛋白水平、20S蛋白酶体的胰凝乳蛋白酶样活性以及Bcl-2相关基因产物-1蛋白水平在5天的HS处理后均短暂升高。因此，这些变化可能是导致5天HS处理后观察到的肌肉质量下降的潜在原因。在整个实验期间，半胱天冬酶-3活性显著增加，而另一种效应半胱天冬酶半胱天冬酶-6和半胱天冬酶-9（半胱天冬酶-3和-6的线粒体依赖性激活剂）的活性仅在10天的HS处理后增加。这表明半胱天冬酶-3可能通过线粒体非依赖性和线粒体依赖性机制在对HS的反应中受到调节。最后，MMP-2/9活性保持不变，而PA活性在5天的HS处理后增加。总体而言，这些数据表明，细胞内和细胞外蛋白酶的时间依赖性调节对于设定大鼠比目鱼肌对HS反应的新表型很重要。
