Mice overexpressing growth hormone exhibit increased skeletal muscle myostatin and MuRF1 with attenuation of muscle mass.
Mice overexpressing growth hormone exhibit increased skeletal muscle myostatin and MuRF1 with attenuation of muscle mass.
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DOI：
10.1186/s13395-017-0133-y
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发表时间：
2017-09-04
期刊：
影响因子：
4.9
通讯作者：
Kopchick JJ
中科院分区：
文献类型：
--
作者：
Consitt LA;Saneda A;Saxena G;List EO;Kopchick JJ
与生长激素(GH)对骨骼肌蛋白质合成的急性影响相比，长期GH治疗对肌肉质量的影响似乎可以忽略不计。尽管有这些知识，但对生长激素对骨骼肌蛋白质合成和萎缩信号通路的慢性影响知之甚少。本研究的目的是确定转基因牛生长激素(BGH)小鼠骨骼肌的蛋白质合成途径是否减弱和/或肌肉萎缩细胞内信号通路是否改变。取5月龄雄性BGH小鼠(n=9)和野生型(WT)对照组(n=9)的腓肠肌和比目鱼肌，分析参与蛋白质合成(Akt/mTOR)、生长和增殖(MAPK)以及肌肉萎缩(MuRF1和myostatin)通路的蛋白质。与WT对照组相比，BGH组小鼠的总体重显著增加(49%，P<；：0.0001)。当相对于总体质量表达时，与对照组相比，过量表达生长激素的小鼠的腓肠肌(− 28%，P<；(0.0001))，但比目鱼肌没有显著降低。与WT仔鼠相比，转基因BGH小鼠的蛋白激酶b(Akt1)、4E结合蛋白1(4E-BP1)、p70S6激酶、p42/44和p38的磷酸化水平升高(P<0.05)。在BGH小鼠中，成熟的肌肉抑制素(26 KDa)、早熟的肌肉抑制素(52 KDa)和激活素受体IIB型(AcvR2B)的蛋白水平增加(P<0.0001)，同时母亲对十碳瘫痪同系物(SMAD2)的磷酸化水平也增加(59%，P<0.0001)。与对照组相比，高表达生长激素的小鼠腓肠肌的MuRF1表达(30%，P<0.05)和胰岛素受体底物1(IRS1)丝氨酸磷酸化(44%，P<0.05)增加，但比目鱼肌没有。这些发现表明，循环中GH的慢性升高对参与骨骼肌蛋白质合成和萎缩的信号通路具有关键影响，并提示在慢性GH/IGF-1过量的环境中，MuRF1、myostatin和IRS1丝氨酸磷酸化可能起到抑制过度糖酵解肌肉生长的作用。
In contrast to the acute effects of growth hormone (GH) on skeletal muscle protein synthesis, long-term GH treatment appears to have negligible effects on muscle mass. Despite this knowledge, little is known regarding the chronic effects of GH on skeletal muscle protein synthesis and atrophy signaling pathways. The purpose of this study was to determine if protein synthesis pathways are attenuated and/or muscle atrophy intracellular signaling pathways are altered in the skeletal muscle of transgenic bovine GH (bGH) mice. The gastrocnemius and soleus from 5-month-old male bGH mice (n = 9) and wild type (WT) controls (n = 9) were harvested and analyzed for proteins involved in the protein synthesis (Akt/mTOR), growth and proliferation (MAPK), and muscle atrophy (MuRF1 and myostatin) pathways. Total body mass was significantly increased in bGH mice compared to WT controls (49%, P < 0.0001). When expressed relative to total body mass, the gastrocnemius (− 28%, P < 0.0001), but not the soleus, was significantly lower in mice overexpressing GH, compared to controls. Transgenic bGH mice had elevated phosphorylation levels of protein kinase b (Akt1), 4E-binding protein 1 (4E-BP1), p70 S6 kinase, p42/44, and p38 (P < 0.05) compared to WT littermates. Mature myostatin (26 kDa), premature myostatin (52 kDa), and activin receptor type IIB (AcvR2B) protein levels were increased in bGH mice (P < 0.05), along with elevated phosphorylation levels of mothers against decapentaplegic homolog (Smad2) (59%, P < 0.0001). Mice overexpressing GH had increased MuRF1 expression (30%, P < 0.05) and insulin receptor substrate 1 (IRS1) serine phosphorylation (44%, P < 0.05) in the gastrocnemius, but not the soleus, when compared to controls. These findings demonstrate that chronic elevations in circulating GH have a critical impact on signaling pathways involved in skeletal muscle protein synthesis and atrophy, and suggest that MuRF1, myostatin, and IRS1 serine phosphorylation may act to inhibit exaggerated glycolytic muscle growth, in environments of chronic GH/IGF-1 excess.
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影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
4.8
作者：
Al-Regaiey, KA;Masternak, MM;Bartke, A
通讯作者：
Bartke, A
DOI：
10.1152/ajpendo.00359.2006
发表时间：
2007-02-01
影响因子：
5.1
作者：
Frost, Robert A.;Nystrom, Gerald J.;Lang, Charles H.
通讯作者：
Lang, Charles H.
影响因子：
3.3
作者：
Harrison, BC;Allen, DL;Leinwand, LA
通讯作者：
Leinwand, LA
DOI：
10.1152/ajpendo.1997.272.1.e94
发表时间：
1997-01-01
影响因子：
5.1
作者：
Butterfield, GE;Thompson, J;Hoffman, AR
通讯作者：
Hoffman, AR