Abstract
Spinal cord injury reduces the rate of skeletal muscle protein synthesis and increases protein breakdown, resulting in rapid muscle loss. The purpose of this study was to determine whether long-term paraplegia would eventually result in a downregulation of muscle mRNA and protein expression associated with both protein synthesis and breakdown. After 10 weeks of spinal cord transection, soleus muscle from 12 rats (6 sham-control, 6 paraplegic) was studied for mRNAs and proteins associated with protein synthesis and breakdown using real-time polymerase chain reaction and immunoblotting techniques. Protein kinase B (PKB/Akt), ribosomal S6 kinase 1 (S6K1), and myogenin mRNA were downregulated, whereas muscle ring finger 1 (MuRF1) and phospho-forkhead transcription factor 4 (FoxO4) protein were increased in paraplegic rats. We conclude that gene and protein expression of pathways associated with protein synthesis are reduced, whereas some markers of protein breakdown remain elevated following chronic paraplegia. Clinical interventions designed to increase muscle protein synthesis may be helpful in preventing excessive muscle loss during long-term paraplegia.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Body Weight
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Insulin-Like Growth Factor I / genetics
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Male
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Muscle Proteins / genetics*
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Muscle Proteins / metabolism*
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Muscle, Skeletal / physiology*
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Muscular Atrophy / metabolism
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Muscular Atrophy / physiopathology*
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Myogenin / genetics
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Myogenin / metabolism
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Myostatin
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Paraplegia / metabolism
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Paraplegia / physiopathology*
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Protein Kinases / genetics
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Proto-Oncogene Proteins c-akt / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Ribosomal Protein S6 Kinases / genetics
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SKP Cullin F-Box Protein Ligases / genetics
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Spinal Cord Injuries / metabolism
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Spinal Cord Injuries / physiopathology
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TOR Serine-Threonine Kinases
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Transforming Growth Factor beta / genetics
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Tripartite Motif Proteins
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
Substances
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Forkhead Transcription Factors
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Mstn protein, rat
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Muscle Proteins
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Myogenin
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Myostatin
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Nerve Tissue Proteins
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RNA, Messenger
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Transforming Growth Factor beta
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Tripartite Motif Proteins
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mechano-growth factor, rat
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Foxo1 protein, rat
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Insulin-Like Growth Factor I
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Fbxo32 protein, rat
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SKP Cullin F-Box Protein Ligases
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Trim63 protein, rat
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Ubiquitin-Protein Ligases
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Protein Kinases
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mTOR protein, rat
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases
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Rps6kb1 protein, rat
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TOR Serine-Threonine Kinases