Differential proteome analysis of aging in rat skeletal muscle
Differential proteome analysis of aging in rat skeletal muscle
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DOI：
10.1096/fj.04-3084fje
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发表时间：
2005-04-01
期刊：
影响因子：
4.8
通讯作者：
Bechet, D
中科院分区：
文献类型：
--
作者：
Piec, I;Listrat, A;Bechet, D
为了确定肌肉衰老的机制，我们进行了高分辨率的差异蛋白质组学分析腓肠肌在年轻的成年人，成年人，和老年LOU/C/Jall大鼠。二维凝胶电泳和随后的MALDI-ToF质谱分析导致40个差异表达的蛋白质的鉴定。引人注目的是，大多数差异的特点是老年（30个月）的动物，而年轻（7个月）和成熟（18个月）的成年人表现出类似的表达模式。收缩蛋白（肌动蛋白、肌球蛋白轻链、肌钙蛋白-T）和细胞骨架蛋白（结蛋白、微管蛋白）以及基本调节蛋白（凝溶胶蛋白、肌球蛋白结合蛋白、CapZ-β、P23）的重要修饰可能导致旧肌力产生和收缩速度的功能障碍。其他特征支持细胞溶质（磷酸丙糖异构酶、烯醇化酶、甘油-3-P脱氢酶、肌酸激酶）和线粒体（异柠檬酸脱氢酶、细胞色素-c氧化酶）能量代谢降低。肌肉老化通常与氧化应激增加有关。因此，我们观察到分子伴侣（热休克蛋白20，热休克蛋白27，网状蛋白ER 60）和蛋白质参与反应性醛解毒（醛脱氢酶，谷胱甘肽转移酶，glycoprotein酶）的差异调节。我们进一步注意到参与转录延伸（RNA加帽蛋白）和RNA编辑（Apobec 2）的蛋白质的上调。这些蛋白质中的大多数以前未被识别为在老年肌肉中差异表达，它们代表了阐明肌肉衰老机制的新起点。
To identify the mechanisms underlying muscle aging, we have undertaken a high-resolution differential proteomic analysis of gastrocnemius muscle in young adults, mature adults, and old LOU/c/jall rats. Two-dimensional gel electrophoresis and subsequent MALDI-ToF mass spectrometry analyses led to the identification of 40 differentially expressed proteins. Strikingly, most differences characterized old (30-month) animals, whereas young (7-month) and mature (18-month) adults exhibited similar patterns of expression. Important modifications in contractile (actin, myosin light-chains, troponins-T) and cytoskeletal (desmin, tubulin) proteins, and in essential regulatory proteins (gelsolin, myosin binding proteins, CapZ-beta, P23), likely account for dysfunctions in old muscle force generation and speed of contraction. Other features support decreases in cytosolic (triose-phosphate isomerase, enolase, glycerol-3-P dehydrogenase, creatine kinase) and mitochondrial (isocitrate dehydrogenase, cytochrome-c oxidase) energy metabolisms. Muscle aging is often associated with increased oxidative stress. Accordingly, we observed differential regulation of molecular chaperones (hsp20, hsp27, reticuloplasmin ER60) and of proteins implicated in reactive aldehyde detoxification (aldehyde dehydrogenase, glutathione transferase, glyoxalase). We further noticed up-regulation of proteins involved in transcriptional elongation (RNA capping protein) and RNA-editing (Apobec2). Most of these proteins were previously unrecognized as differentially expressed in old muscles, and they represent novel starting points for elucidating the mechanisms of muscle aging.