Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
J Proteomics. 2010 Jun 16;73(8):1441-53. doi: 10.1016/j.jprot.2010.01.014. Epub 2010 Feb 11.
Contractile weakness and loss of muscle mass are critical features of the aging process in mammalians. Age-related fibre wasting has a profound effect on muscle metabolism, fibre type distribution and the overall physiological integrity of the neuromuscular system. This study has used mass spectrometry-based proteomics to investigate the fate of the aging rat muscle proteome. Using nonionic detergent phase extraction, this report shows that the aged gastrocnemius muscle exhibits a generally perturbed protein expression pattern in both the detergent-extracted fraction and the aqueous protein complement from senescent muscle tissue. In the detergent-extracted fraction, the expression of ATP synthase, isocitrate dehydrogenase, enolase, tropomyosin and beta-actin was increased. Different isoforms of creatine kinase and prohibitin showed differential changes. In the aqueous fraction, malate dehydrogenase, sulfotransferase, triosephosphate isomerase, aldolase, cofilin-2 and lactate dehydrogenase showed increased levels. Interestingly, differential effects on dissimilar 2-D spots of the same protein species were shown for Cu/Zn superoxide dismutase, albumin, annexin A4 and phosphoglycolate phosphatase. Mitochondrial Hsp60, Hsp71 and nucleoside diphosphate kinase B exhibited a reduced abundance in aged muscle. The majority of altered proteins were found to be involved in mitochondrial metabolism, glycolysis, metabolic transportation, regulatory processes, the cellular stress response, detoxification mechanisms and muscle contraction.
收缩无力和肌肉质量的丧失是哺乳动物衰老过程中的关键特征。与年龄相关的纤维消耗对肌肉代谢、纤维类型分布和神经肌肉系统的整体生理完整性有深远的影响。本研究使用基于质谱的蛋白质组学来研究衰老大鼠肌肉蛋白质组的命运。本报告采用非离子型去污剂相萃取法表明，衰老的比目鱼肌在去污剂提取部分和衰老肌肉组织的水性蛋白质成分中表现出普遍失调的蛋白质表达模式。在去污剂提取部分，ATP 合酶、异柠檬酸脱氢酶、烯醇酶、原肌球蛋白和β-肌动蛋白的表达增加。肌酸激酶和抑制素的不同同工型显示出不同的变化。在水性部分，苹果酸脱氢酶、磺基转移酶、三磷酸甘油异构酶、醛缩酶、肌动蛋白抑制蛋白-2 和乳酸脱氢酶的水平升高。有趣的是，铜/锌超氧化物歧化酶、白蛋白、膜联蛋白 A4 和磷酸甘油酸磷酸酶的同一蛋白质种类的不同 2-D 斑点显示出不同的差异效应。线粒体 Hsp60、Hsp71 和核苷二磷酸激酶 B 在衰老肌肉中的丰度降低。大多数改变的蛋白质被发现参与线粒体代谢、糖酵解、代谢运输、调节过程、细胞应激反应、解毒机制和肌肉收缩。
