Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size through expression profiling. Am J Physiol Regul Integr Comp Physiol 2008 Oct;295(4):R1263-73
Date
08/30/2008Pubmed ID
18753264Pubmed Central ID
PMC2576097DOI
10.1152/ajpregu.90455.2008Scopus ID
2-s2.0-57349185907 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
Changes in gene expression associated with skeletal muscle atrophy due to aging are distinct from those due to disuse, suggesting that the response of old muscle to inactivity may be altered. The goal of this study was to identify changes in muscle gene expression that may contribute to loss of adaptability of old muscle. Muscle atrophy was induced in young adult (6-mo) and old (32-mo) male Brown Norway/F344 rats by 2 wk of hindlimb suspension (HS), and soleus muscles were analyzed by cDNA microarrays. Overall, similar changes in gene expression with HS were observed in young and old muscles for genes encoding proteins involved in protein folding (heat shock proteins), muscle structure, and contraction, extracellular matrix, and nucleic acid binding. More genes encoding transport and receptor proteins were differentially expressed in the soleus muscle from young rats, while in soleus muscle from old rats more genes that encoded ribosomal proteins were upregulated. The gene encoding the cold-shock protein RNA-binding motif protein-3 (RBM3) was induced most highly with HS in muscle from old rats, verified by real-time RT-PCR, while no difference with age was observed. The cold-inducible RNA-binding protein (Cirp) gene was also overexpressed with HS, whereas cold-shock protein Y-box-binding protein-1 was not. A time course analysis of RBM3 mRNA abundance during HS showed that upregulation occurred after apoptotic nuclei and markers of protein degradation increased. We conclude that a cold-shock response may be part of a compensatory mechanism in muscles undergoing atrophy to preserve remaining muscle mass and that RBM3 may be a therapeutic target to prevent muscle loss.
Author List
Dupont-Versteegden EE, Nagarajan R, Beggs ML, Bearden ED, Simpson PM, Peterson CAAuthor
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age FactorsAnimals
DNA-Binding Proteins
Down-Regulation
Endosomal Sorting Complexes Required for Transport
Gene Expression Profiling
Hindlimb Suspension
Male
Muscle Proteins
Muscle, Skeletal
Muscular Atrophy
Nedd4 Ubiquitin Protein Ligases
Proto-Oncogene Proteins c-bcl-2
RNA-Binding Proteins
Rats
Rats, Inbred BN
Rats, Inbred F344
SKP Cullin F-Box Protein Ligases
Tripartite Motif Proteins
Ubiquitin-Protein Ligases
Up-Regulation
X-Linked Inhibitor of Apoptosis Protein
