Regulation of myogenin protein expression in denervated muscles from young and old rats

Regulation of myogenin protein expression in denervated muscles from young and old rats
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DOI:
10.1152/ajpregu.2000.279.1.r179
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发表时间:
2000-07-01
影响因子:
2.8
通讯作者:
Goldman, D
Goldman, D
中科院分区:
医学3区
文献类型:
--
作者:
Kostrominova, TY;Macpherson, PCD;Goldman, D

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肌原素是一种肌肉特异性转录因子,参与去神经支配诱导的烟碱乙酰胆碱受体(nAChR)基因表达的增加。虽然在去神经支配肌肉中肌原蛋白RNA的表达是有充分记录的,但令人惊讶的是,关于肌原蛋白的表达却知之甚少。因此,我们检测了幼龄(4个月)和老年(24-32个月)大鼠神经支配和去神经支配肌肉中的肌原素蛋白和RNA,并将其表达与nAChR α亚基RNA的表达进行了比较。这些实验显示,肌原蛋白表达在去神经支配1天内增加,在可检测到的nAChR RNA增加之前。去神经支配3天后,肌原素和nAChR α亚基RNA分别增加了500倍和130倍,而肌原素蛋白增加了14倍。有趣的是,老年大鼠(32个月)的肌原蛋白水平比年轻大鼠高6倍,mRNA水平比年轻大鼠高80倍。然而,在去神经支配后,幼龄和老年动物的表达水平相似。衰老过程中肌原蛋白表达的增加,往往局限于小纤维,可能反映了自发的去神经支配和/或再生。我们的研究结果表明,去神经支配肌肉中肌原蛋白的增加与其mRNA的上调有关。
Myogenin is a muscle-specific transcription factor participating in denervation-induced increases in nicotinic ACh receptor (nAChR) gene expression. Although myogenin RNA expression in denervated muscle is well documented, surprisingly little is known about myogenin protein expression. Therefore, we assayed myogenin protein and RNA in innervated and denervated muscles from young (4 mo) and old (24-32 mo) rats and compared this expression to that of the nAChR alpha-subunit RNA. These assays revealed increased myogenin protein expression within 1 day of denervation, preceding detectable increases in nAChR RNA. By 3 days of denervation, myogenin and nAChR alpha-subunit RNA were increased 500- and 130-fold, respectively, whereas myogenin protein increased 14-fold. Interestingly, old rats (32 mo) had 6-fold higher myogenin protein and similar to 80-fold higher mRNA levels than young rats. However, after denervation, expression levels were similar for young and old animals. The increased myogenin expression during aging, which tends to localize to small fibers, likely reflects spontaneous denervation and/or regeneration. Our results show that increased myogenin protein in denervated muscles correlates with the upregulation of its mRNA.