Involvement of eukaryotic translation initiation factor 5A (eIF5A) in skeletal muscle stem cell differentiation.
The eukaryotic translation initiation factor 5A (eIF5A) contains a special amino acid residue named hypusine that is required for its activity, being produced by a post-translational modification using spermidine as substrate. Stem cells from rat skeletal muscles (satellite cells) were submitted to differentiation and an increase of eIF5A gene expression was observed. Higher content of eIF5A protein was found in satellite cells on differentiation in comparison to non-differentiated satellite cells and skeletal muscle. The treatment with N1-guanyl-1,7-diaminoheptane (GC7), a hypusination inhibitor, reversibly abolished the differentiation process. In association with the differentiation blockage, an increase of glucose consumption and lactate production and a decrease of glucose and palmitic acid oxidation were observed. A reduction in cell proliferation and protein synthesis was also observed. L-Arginine, a spermidine precursor and partial suppressor of muscle dystrophic phenotype, partially abolished the GC7 inhibitory effect on satellite cell differentiation. These results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle regeneration.
Luchessi
Augusto D
AD
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. luchessi@icb.usp.br
Cambiaghi
Tavane D
TD
Hirabara
Sandro M
SM
Lambertucci
Rafael H
RH
Silveira
Leonardo R
LR
Baptista
Igor L
IL
Moriscot
Anselmo S
AS
Costa-Neto
Claudio M
CM
Curi
Rui
R
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D064211:Connectin; D005786:Gene Expression Regulation / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000097574:Eukaryotic Translation Initiation Factor 5A
D001120:Arginine; D002843:Chromatin; D064211:Connectin; D006147:Guanine; D008239:Lysine; D009124:Muscle Proteins; D017570:MyoD Protein; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C057363:MyoD1 myogenic differentiation protein; C100667:N(1)-guanyl-1,7-diaminoheptane; C100028:hypusine