Chen Yi-Wen, Nader Gustavo A, Baar Keith R, Fedele Mark J, Hoffman Eric P, Esser Karyn A
Research Center for Genetic Medicine, Children's National Medical Center and George Washington University, Washington DC, USA.
J Physiol. 2002 Nov 15;545(1):27-41. doi: 10.1113/jphysiol.2002.021220.
To further understand molecular mechanisms underlying skeletal muscle hypertrophy, expression profiles of translationally and transcriptionally regulated genes were characterized following an acute bout of maximally activated eccentric contractions. Experiments demonstrated that translational mechanisms contribute to acute gene expression changes following high resistance contractions with two candidate mRNAs, basic fibroblast growth factor (bFGF) and elongation factor-1 alpha (EF1alpha), targeted to the heavier polysomal fractions after a bout of contractions. Gene profiling was performed using Affymetrix Rat U34A GeneChips with either total RNA or polysomal RNA at one and six hours following contractions. There were 18 genes that changed expression at one hour and 70 genes that were different (60 genes increased:10 genes decreased)at six hours after contractions. The model from this profiling suggests that following high resistance contractions skeletal muscle shares a common growth profile with proliferating cells exposed to serum. This cluster of genes can be classified as "growth" genes and is commonly associated with progression of the cell cycle. However, a unique aspect was that there was induction of a cluster of tumour suppressor or antigrowth genes. We propose that this cluster of "antigrowth" genes is induced by the stress of contractile activity and may act to maintain skeletal muscle in the differentiated state. From the profiling results, further experiments determined that p53 levels increased in skeletal muscle at 6 h following contractions. This novel finding of p53 induction following exercise also demonstrates the power of expression profiling for identification of novel pathways involved in the response to muscle contraction.
为了进一步了解骨骼肌肥大背后的分子机制，在一次最大激活的离心收缩急性发作后，对翻译和转录调控基因的表达谱进行了表征。实验表明，翻译机制有助于高阻力收缩后急性基因表达的变化，两种候选mRNA，即碱性成纤维细胞生长因子（bFGF）和延伸因子-1α（EF1α），在一次收缩后靶向较重的多核糖体组分。在收缩后1小时和6小时，使用Affymetrix大鼠U34A基因芯片对总RNA或多核糖体RNA进行基因谱分析。收缩后1小时有18个基因表达发生变化，6小时有70个基因不同（60个基因增加：10个基因减少）。该分析模型表明，高阻力收缩后，骨骼肌与暴露于血清的增殖细胞具有共同的生长谱。这一组基因可归类为“生长”基因，通常与细胞周期进程相关。然而，一个独特的方面是诱导了一组肿瘤抑制或抗生长基因。我们提出，这一组“抗生长”基因是由收缩活动的应激诱导的，可能起到维持骨骼肌分化状态的作用。根据分析结果，进一步的实验确定收缩后6小时骨骼肌中p53水平升高。运动后p53诱导这一新颖发现也证明了表达谱分析在识别参与肌肉收缩反应的新途径方面的作用。
