Comparative proteomic analysis of the aging soleus and extensor digitorum longus rat muscles using TMT labeling and mass spectrometry.

Comparative proteomic analysis of the aging soleus and extensor digitorum longus rat muscles using TMT labeling and mass spectrometry.
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DOI:
10.1021/pr400644x
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发表时间:
2013-10-04
影响因子:
4.4
通讯作者:
Lancha AH Jr
Lancha AH Jr
中科院分区:
生物学2区
文献类型:
--
作者:
Chaves DF;Carvalho PC;Lima DB;Nicastro H;Lorenzeti FM;Siqueira-Filho M;Hirabara SM;Alves PH;Moresco JJ;Yates JR 3rd;Lancha AH Jr

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骨骼肌减少症是指骨骼肌质量、力量和功能与年龄相关的下降,最终损害新陈代谢,导致平衡能力差、经常跌倒、活动能力受限和生活质量下降。在这里,我们通过蛋白质组学鸟枪法研究肌肉减少症的发病机制。简单地说,我们使用串联质量标签(TMT)来定量和比较从年轻和年老的大鼠慢抽动型肌肉(比目鱼肌)和快速抽动型肌肉(指长伸肌,EDL)中获得的蛋白质谱。我们的研究结果揭示了从比目鱼和EDL肌肉样本中鉴定出的3452和1848蛋白,其中分别发现了78和174个差异表达。一般来说,大多数蛋白质是结构相关的,参与能量代谢、氧化应激、解毒或运输。衰老对比目鱼肌和EDL肌的影响不同,几种蛋白质以相反的方式调节。例如,丙酮酸激酶在比目鱼肌和EDL肌中的表达和活性不同。我们能够用现有文献验证我们的许多差异表达蛋白作为候选衰老生物标志物,最重要的是,揭示了一些新的候选生物标志物,如胶质母细胞瘤扩增序列(GAS),零β -球蛋白和prolargin。
Sarcopenia describes an age-related decline in skeletal muscle mass, strength, and function that ultimately impairs metabolism, leads to poor balance, frequent falling, limited mobility, and a reduction in quality of life. Here we investigate the pathogenesis of sarcopenia through a proteomic shotgun approach. Briefly, we employed tandem mass tags (TMT) to quantitate and compare the protein profiles obtained from young versus old rat slow-twitch type of muscle (soleus) and a fast-twitch type of muscle (extensor digitorum longus, EDL). Our results disclose 3452 and 1848 proteins identified from soleus and EDL muscles samples of which 78 and 174 were found to be differentially expressed, respectively. In general, most of the proteins were structural related, involved in energy metabolism, oxidative stress, detoxification, or transport. Aging affected soleus and EDL muscles differently and several proteins were regulated in opposite ways. For example, pyruvate kinase had its expression and activity different in both soleus and EDL muscles. We were able to verify with existing literature many of our differentially expressed proteins as candidate aging biomarkers, and most importantly, disclose several new candidate biomarkers such as the glioblastoma amplified sequence (GAS), zero beta-globin, and prolargin.
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