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Doctoral Thesis
DOI
10.11606/T.42.2007.tde-04102007-095125
Document
Author
Full name
Augusto Ducati Luchessi
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Curi, Rui (President)
Carvalho, Carla Roberta de Oliveira
Hirabara, Sandro Massao
Hirata, Mario Hiroyuki
Silveira, Leonardo dos Reis
Title in Portuguese
Envolvimento do fator de início de tradução de eucariotos 5A (elF5A) na diferenciação de células-tronco da musculatura esquelética
Abstract in Portuguese
A proteína eIF5A apresenta um resíduo exclusivo de aminoácido chamado hipusina formado por modificação pós-traducional envolvendo espermidina como substrato. Neste estudo, observamos que a expressão de eIF5A é intensificada ao longo da diferenciação de células-tronco progenitoras de fibras musculares (células satélites) e que a inibição da hipusinação com GC7 bloqueia a diferenciação. Associado a esse bloqueio encontramos aumento do consumo de glicose e produção de lactato, diminuição da descarboxilação de glicose e palmitato, redução da proliferação celular e alteração do perfil traducional, efeitos que podem estar envolvidos na inibição do programa de diferenciação. Em seguida, o músculo tibial anterior de ratos foram criolesados e após severa supressão da expressão de eIF5A (período agudo de lesão) a mesma foi retomada ao longo da regeneração, chegando a quantidades superiores ao encontrado em músculos não lesados. Verificamos que a L-arginina, um supressor parcial do fenótipo distrófico e precursor de espermidina, reverte parcialmente o efeito de GC7.
Title in English
Involvement of eukaryotic translation initiation factor 5a (eif5a) in skeletal muscle stem cell differentiation.
Keywords in English
Bacteria de rizosfera
Cana de açúcar transgênica
Cell Biochemistry
Cell Differentiation
DGGE (Gradiente desnaturante em gel de eletrofore)
Diversidade bacteriana
Diversidade fisiológica
eIF5A
Herbicida
Muscle Differentiation
Satellite Cells
Stem Cells
Abstract in English
eIF5A protein contains an exclusive amino acid residue named hypusine produced by a post-translational modification involving spermidine as substrate. In this study, we observed that eIF5A expression is raised during muscle fiber stem cells (satellite cells) differentiation and the hypusination inhibition by GC7 abolished the differentiation process. In association with this blockage, an increase in glucose consumption and lactate production, a decrease in glucose and palmitate decarboxylation, a reduction in cell proliferation and an alteration in translational profile were observed. These changes may be involved in the inhibition of the differentiation induced by GC7. The rat tibialis anterior muscle was injured and a marked reduction of eIF5A expression (acute injury period) was found. The expression of eIF5A was reestablished during regeneration, reaching higher levels than that observed in non injured muscle. We also verified that L-arginine, a partial suppressor of muscle dystrophic phenotype condition and precursor of spermidine, partially abolished the GC7 effects.
 
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Anexo_A.pdf (226.56 Kbytes)
Anexo_B.pdf (148.79 Kbytes)
Anexo_C.pdf (392.85 Kbytes)
TDE_2007_01.pdf (2.39 Mbytes)
Publishing Date
2007-10-04
 
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