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2030-01-01
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β-HYDROXY-β-METHYLBUTYRATE (HMB) STIMULATES MYOGENIC CELL PROLIFERATION, DIFFERENTIATION AND SURVIVAL VIA THE MAPK/ERK AND PI3K/AKT PATHWAYS
Mioblastos
roteínas Proto-Oncogênicas c-akt
Apoptose
Proliferação
Diferenciação
Músculo Esquelético
Affilliation
The Hebrew University of Jerusalem. Department of Animal Sciences. Jerusalem, Israel.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France.
The Hebrew University of Jerusalem. Department of Animal Sciences. Jerusalem, Israel.
The Hebrew University of Jerusalem. Department of Animal Sciences. Jerusalem, Israel.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France.
Université Pierre et Marie Curie Paris 06. INSERM UMR S 787. Institut de Myologie. 105 bd de l'hôpital 75634. Paris Cedex 13, France.
The Hebrew University of Jerusalem. Department of Animal Sciences. Jerusalem, Israel.
The Hebrew University of Jerusalem. Department of Animal Sciences. Jerusalem, Israel.
Abstract
β-hydroxy-β-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced
protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell
proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellitecell
depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serumstarved
myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/
ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion.
Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells,
reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry
analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB
enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated
Akt phosphorylation on Thr308 and Ser473 and this was inhibited byWortmannin, suggesting that HMB acts
via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in
mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB
on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive
influence in preventing muscle wasting.
DeCS
Ácido DesidrocólicoMioblastos
roteínas Proto-Oncogênicas c-akt
Apoptose
Proliferação
Diferenciação
Músculo Esquelético
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