Clenbuterol induces muscle-specific attenuation of atrophy through effects on the ubiquitin-proteasome pathway.
Clenbuterol induces muscle-specific attenuation of atrophy through effects on the ubiquitin-proteasome pathway.
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DOI：
10.1152/japplphysiol.00448.2004
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发表时间：
2005-07
影响因子：
3.3
通讯作者：
T. Yimlamai;S. Dodd;S. Borst;Sooyeon Park
中科院分区：
文献类型：
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作者：
T. Yimlamai;S. Dodd;S. Borst;Sooyeon Park
泛素-蛋白酶体途径主要负责后肢减重（HU）过程中的肌原纤维蛋白降解。β-肾上腺素能激动剂，如克伦特罗（CB）诱导肌肉肥大和减弱肌肉萎缩，由于废用或不活动。然而，CB发挥这些作用的分子机制仍然知之甚少。本研究的目的是调查CB是否通过抑制泛素-蛋白酶体途径来减弱HU诱导的肌肉萎缩，以及胰岛素样生长因子I（IGF-I）是否介导这种抑制。将大鼠随机分为以下组：负重对照组、14天CB处理组、14天HU组和CB + HU组。HU诱导的萎缩与蛋白水解增加和泛素-蛋白酶体途径组分（泛素结合物、泛素结合酶E2-14 kDa和20 S蛋白酶体活性）上调相关。泛素蛋白酶体的上调发生在所有的肌肉测试，但更明显的主要由慢肌纤维（比目鱼肌）比快肌（跖肌和胫骨前肌）。虽然CB引起的肥大在所有的肌肉，CB衰减胡诱导的萎缩和减少泛素结合物只在快速足底肌和胫骨前肌，而不是在慢比目鱼肌。CB没有提高IGF-I蛋白质含量在任何肌肉检查。这些结果表明，CB诱导肥大和抑制HU诱导的萎缩，特别是在快肌中，至少部分通过肌肉特异性抑制泛素-蛋白酶体途径，并且这些作用不由骨骼肌中IGF-I的局部产生介导。
The ubiquitin-proteasome pathway is primarily responsible for myofibrillar protein degradation during hindlimb unweighting (HU). Beta-adrenergic agonists such as clenbuterol (CB) induce muscle hypertrophy and attenuate muscle atrophy due to disuse or inactivity. However, the molecular mechanism by which CB exerts these effects remains poorly understood. The aims of this study were to investigate whether CB attenuates HU-induced muscle atrophy through an inhibition of the ubiquitin-proteasome pathway and whether insulin-like growth factor I (IGF-I) mediates this inhibition. Rats were randomized to the following groups: weight-bearing control, 14-day CB-treated, 14-day HU, and CB + HU. HU-induced atrophy was associated with increased proteolysis and upregulation of components of the ubiquitin-proteasome pathway (ubiquitin conjugates, ubiquitin conjugating enzyme E2-14 kDa, and 20S proteasome activity). Upregulation of the ubiquitin proteasome occurred in all muscles tested but was more pronounced in muscles composed primarily of slow-twitch fibers (soleus) than in fast-twitch muscles (plantaris and tibialis anterior). Although CB induced hypertrophy in all muscles, CB attenuated the HU-induced atrophy and reduced ubiquitin conjugates only in the fast plantaris and tibialis anterior and not in the slow soleus muscle. CB did not elevate IGF-I protein content in either of the muscles examined. These results suggest that CB induces hypertrophy and alleviates HU-induced atrophy, particularly in the fast muscles, at least in part through a muscle-specific inhibition of the ubiquitin-proteasome pathway and that these effects are not mediated by the local production of IGF-I in skeletal muscle.