Department of Molecular Biosciences and Bioengineering, University of Hawaii, Honolulu, Hawaii, USA.
Muscle Nerve. 2011 May;43(5):700-7. doi: 10.1002/mus.21950. Epub 2011 Apr 1.
In this study we investigated the combined effect of myostatin (MSTN) suppression and β-agonist (clenbuterol) administration on muscle hypertrophy and the phosphorylation of muscle 4E-BP1 and p70S6k, two downstream effectors of the Akt/mTOR anabolic pathway.
Female heterozygous MSTN-prodomain transgenic mice (an MSTN suppression model) and wild-type littermates were given 0 or 20 ppm of clenbuterol (CL) in their drinking water, and muscle samples were collected at 1 and 2 weeks after treatment.
CL increased body and muscle mass in both genotypes. Levels of phosphorylated muscle 4E-BP1 and p70S6k were higher in MSTN-prodomain transgenic mice than in wild-type mice. CL increased the phosphorylation of 4E-BP1 and p70S6k in both genotypes.
The muscle-hypertrophic effect of CL is additive to the effect of MSTN suppression. The combination of MSTN suppression and treatment with β-agonists may be an effective therapeutic approach to combat muscle-wasting conditions.
在这项研究中,我们研究了抑制肌肉生长抑制素(MSTN)和β-激动剂(克仑特罗)给药对肌肉肥大以及 Akt/mTOR 合成途径的两个下游效应物 4E-BP1 和 p70S6k 的磷酸化的联合影响。
雌性杂合 MSTN-前导肽转基因小鼠(MSTN 抑制模型)和野生型同窝仔鼠分别给予 0 或 20ppm 的克仑特罗(CL)在饮用水中,并在治疗后 1 周和 2 周收集肌肉样本。
CL 增加了两种基因型的体重和肌肉量。磷酸化肌肉 4E-BP1 和 p70S6k 的水平在 MSTN-前导肽转基因小鼠中高于野生型小鼠。CL 增加了两种基因型中 4E-BP1 和 p70S6k 的磷酸化。
CL 的肌肉肥大效应是对 MSTN 抑制效应的附加作用。抑制 MSTN 与β-激动剂治疗的结合可能是对抗肌肉消耗疾病的有效治疗方法。