Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice
Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice
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DOI：
10.1152/ajpendo.90862.2008
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发表时间：
2009-03-01
影响因子：
5.1
通讯作者：
Mehta, Sangeeta
中科院分区：
文献类型：
--
作者：
Welle, Stephen;Burgess, Kerri;Mehta, Sangeeta
well S, Burgess K, Mehta S.通过抑制肌生长抑制素刺激成熟小鼠骨骼肌肌原纤维蛋白合成、p70 S6激酶磷酸化和核糖体蛋白S6磷酸化。[J] .中国生物医学工程学报，2009,31(2):567- 572。首次发表于2009年1月13日；doi: 10.1152 / ajpendo.90862.2008。在发育过程中破坏肌肉生长抑制素的活性会增加肌肉蛋白质合成的速度。本研究旨在确定发育后肌生长抑制素活性的丧失是否会刺激肌原纤维蛋白的合成以及一些参与蛋白质合成速率调节的蛋白质的磷酸化。通过注射抗肌生长抑制素抗体（JA16）， 4 ~ 5龄雄性小鼠的肌生长抑制素活性被抑制4天。通过掺入氘标记苯丙氨酸测定，与盐水处理小鼠相比，平均肌纤维合成率提高了19% （P < 0.01）。JA16上调p70 S6激酶（S6K）和核糖体蛋白S6 （rpS6）磷酸化1.9倍（P < 0.05）。它不影响真核起始因子4e结合蛋白1或Akt的磷酸化。微阵列和实时PCR分析表明，JA16没有选择性地增加编码肌原纤维蛋白、核糖体蛋白或翻译起始因子和延伸因子的mrna水平。不管小鼠是否注射了JA16，雷帕霉素治疗都没有影响肌原纤维蛋白的合成速度，尽管它消除了S6K和rpS6的磷酸化。我们得出结论，成熟肌肉中正常水平的肌肉生长抑制素活性足以抑制肌原纤维合成速率和S6K和rpS6的磷酸化。用抗肌生长抑制素抗体逆转对肌纤维合成的抑制并不依赖于mTOR的激活。
Welle S, Burgess K, Mehta S. Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice. Am J Physiol Endocrinol Metab 296: E567-E572, 2009. First published January 13, 2009; doi:10.1152/ajpendo.90862.2008.-Knocking out myostatin activity during development increases the rate of muscle protein synthesis. The present study was done to determine whether postdevelopmental loss of myostatin activity stimulates myofibrillar protein synthesis and the phosphorylation of some of the proteins involved in regulation of protein synthesis rate. Myostatin activity was inhibited for 4 days, in 4- to 5-mo-old male mice, with injections of an anti-myostatin antibody (JA16). The mean myofibrillar synthesis rate increased 19% (P < 0.01) relative to the mean rate in saline-treated mice, as determined by incorporation of deuterium-labeled phenylalanine. JA16 increased phosphorylation of p70 S6 kinase (S6K) and ribosomal protein S6 (rpS6) 1.9-fold (P < 0.05). It did not affect phosphorylation of eukaryotic initiation factor 4E-binding protein-1 or Akt. Microarrays and real-time PCR analyses indicated that JA16 administration did not selectively enrich levels of mRNAs encoding myofibrillar proteins, ribosomal proteins, or translation initiation and elongation factors. Rapamycin treatment did not affect the rate of myofibrillar protein synthesis whether or not the mice received JA16 injections, although it eliminated the phosphorylation of S6K and rpS6. We conclude that the normal level of myostatin activity in mature muscle is sufficient to inhibit myofibrillar synthesis rate and phosphorylation of S6K and rpS6. Reversal of the inhibition of myofibrillar synthesis with an anti-myostatin antibody is not dependent on mTOR activation.