Opposite pathobiochemical fate of pyruvate kinase and adenylate kinase in aged rat skeletal muscle as revealed by proteomic DIGE analysis

Doran, Philip and O'Connell, Kathleen and Gannon, Joan and Kavanagh, Marcella and Ohlendieck, Kay (2008) Opposite pathobiochemical fate of pyruvate kinase and adenylate kinase in aged rat skeletal muscle as revealed by proteomic DIGE analysis. Proteomics, 8 (2). pp. 364-377. ISSN 1615-9853

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Sarcopenia is the drastic loss of skeletal muscle mass and strength during ageing. In order to better understand the molecular pathogenesis of age-related muscle wasting, we have performed a DIGE analysis of young adult versus old rat skeletal muscle. Proteomic profiling revealed that out of 2493 separated 2-D spots, 69 proteins exhibited a drastically changed expression. Age-dependent alterations in protein abundance indicated dramatic changes in metabolism, contractile activity, myofibrillar remodelling and stress response. In contrast to decreased levels of pyruvate kinase (PK), enolase and phosphofructokinase, the mitochondrial ATP synthase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and adenylate kinase (AK) were increased in senescent fibres. Higher expression levels of myoglobin and fatty acid binding-protein indicated a shift to more aerobic-oxidative metabolism in a slower-twitching aged fibre population. The drastic increase in alphaB-crystallin and myotilin demonstrated substantial filament remodelling during ageing. An immunoblotting survey of selected muscle proteins confirmed the pathobiochemical transition process in aged muscle metabolism. The proteomic analysis of aged muscle has identified a large cohort of new biomarkers of sarcopenia including opposite changes in PK and AK, which might be useful for the design of improved diagnostic procedures and/or therapeutic strategies to counteract ageing-induced muscle degeneration.

Item Type: Article
Keywords: Ageing; DIGE; Fibre transition; Sarcopenia; Skeletal muscle proteomics;
Academic Unit: Faculty of Science and Engineering > Biology
Item ID: 7497
Identification Number: 10.1002/pmic.200700475
Depositing User: Prof. Kay Ohlendieck
Date Deposited: 07 Oct 2016 10:40
Journal or Publication Title: Proteomics
Publisher: Wiley
Refereed: Yes
Funders: Science Foundation Ireland (SFI), Health Research Board (HRB)

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