Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats
Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats
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DOI：
10.1016/j.nutres.2012.07.005
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发表时间：
2012-09-01
影响因子：
4.5
通讯作者：
Okimura, Yasuhiko
中科院分区：
文献类型：
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作者：
Maki, Taiki;Yamamoto, Daisuke;Okimura, Yasuhiko
Atrogin-1和MuRF 1，肌肉特异性泛素连接酶和自噬在肌肉中的蛋白质降解中发挥作用。我们假设支链氨基酸（BCAAs）可以减少atrogin-1，MuRF 1和自噬，并可能对废用性肌肉萎缩有保护作用。为了验证这一假设，我们选择后肢悬吊（HS）诱导的肌肉萎缩作为废用性肌肉萎缩的模型，因为它是一个建立的模型，以研究肌肉活动减少的影响。将Sprague-Dawley雄性大鼠分为4组：对照组、HS组（14天）、口服BCAA给药组（600 mg/[kg/天]，22.9% L-异亮氨酸、45.8% L-亮氨酸和27.6% L-缬氨酸）以及HS和BCAA给药组。处理14天后，测量肌肉重量和蛋白质浓度、肌纤维横截面积（CSA）、atrogin-1和MuRF 1蛋白以及微管相关蛋白1轻链3 II/I（LC 3 II/I的比率）。后肢悬吊显著降低比目鱼肌重量和肌纤维横截面积。支链氨基酸的管理部分，但显着逆转HS诱导的CSA减少。后肢悬吊增加了atrogin-1和MuRF 1蛋白，它们在各种肌肉萎缩中起着关键作用。支链氨基酸减弱了比目鱼肌中atrogin-1和MuRF 1的增加。后肢悬吊显著增加了LC 3 II/I的比率，这是自噬的一个指标，而BCAA并没有减弱LC 3 II/I比率的增加。这些结果表明BCAA至少部分通过抑制遍在蛋白-蛋白酶体途径来抑制HS诱导的肌肉萎缩的可能性。口服支链氨基酸似乎有可能防止废用性肌肉萎缩。(C)2012 Elsevier Inc. All rights reserved.
Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)-induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% L-isoleucine, 45.8% L-leucine, and 27.6% L-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy. (C) 2012 Elsevier Inc. All rights reserved.