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- W2039346988 abstract "INTRODUCTION Animal models of skeletal muscle atrophy have identified increased expression of the metalloproteinases (MMPs) when a limb is immobilized. It has been suggested that these protein products affect the stability of the extracellular matrix (ECM) and induce protein degradation via upregulation of the ubiquitin proteasome pathway. PURPOSE This study was designed to investigate gene expression of MMPs and ubiquitin proteases following 48h of knee immobilization in humans. METHODS To induce atrophy, the dominant leg of five men, 20.4 ± 0.5 years, was immobilized for 48h in a brace that extended from below the groin to the ankle. The brace fixed the knee angle at 160°. A percutaneous needle biopsy was taken from the vastus lateralis muscle ten days before and immediately after immobilization. Gene expression analysis was performed on muscle biopsies using Human U133 Affymetrix gene chips. Targeted confirmation of protein products for genes of interest are currently being performed on muscle biopsy tissue using western blotting techniques and/or immunohistochemistry. RESULTS Ubiquitin specific proteases (FBX09, FBX032, PSME4, USP 14, USP 33, USP 48) were upregulated 1.4 to 1.9 fold (p<0.01). Matrix metalloproteinases (ADAM9, MMEL2,) were upregulated 1.4 to 1.9 fold (p<0.01), and inhibitors of MMP activity (ADAM28, TIMP1) were down regulated −1.8 to −2.6 fold (p<0.01). An unexpected finding was that several genes in the metallothionein family (MT1E, MT1F MT1H, MT1X) were upregulated 1.8–2.3 fold (p<0.01). CONCLUSIONS These data demonstrate that 48h of knee immobilization induces the expression of MMPs and ubiquitin specific proteases. It is likely that an inability to regulate MMPs when a limb is immobilized is related to ECM damage and the subsequent activation of proteolytic pathways in skeletal muscle. These events likely trigger the increased activity of the metallothioneins, which function to protect the cell in response to damage. Supported by the American College of Sports Medicine/EAS Research Grant on Sports Nutrition and Human Performance." @default.
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- W2039346988 date "2005-05-01" @default.
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- W2039346988 title "Matrix Metalloproteinase, Ubiquitin Proteasome, And Metallothionein Gene Expression Following 48h Knee Immobilization In Humans" @default.
- W2039346988 doi "https://doi.org/10.1097/00005768-200505001-00400" @default.
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