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β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells

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Salto González, R.; et al. β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells. Plos One, 10(8): e0135614 (2015). [http://hdl.handle.net/10481/37312]

1932-6203

http://hdl.handle.net/10481/37312

10.1371/journal.pone.0135614

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(Ilíberis: fondo bibliográfico histórico de la Universidad de Granada)

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Title:: β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells
Tema:: Neurites; Neuronal differentiation; Neurons; Protein synthesis; Neuronal plasticity; Cell differentiation; Muscle differentiation; Phosphorylation
Description:: β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.; This project has been funded by Abbott Nutrition R&D.
Idioma:: English
Autor/Productor:: Salto González, Rafael; Vílchez Rienda, José Dámaso; Girón González, María Dolores; Cabrera, Elena; Campos, Nefertiti; Manzano, Manuel; Rueda Cabrera, Ricardo; López-Pedrosa, José M.
Publisher:: Public Library of Science (PLOS)
Rights:: Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License; http://creativecommons.org/licenses/by-nc-nd/3.0/; info:eu-repo/semantics/openAccess
Date:: 2015-09-09T09:50:55Z; 2015
Tipo de recurso:: info:eu-repo/semantics/article

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1. <dc:title>β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells</dc:title>
2. <dc:creator>Salto González, Rafael</dc:creator>
3. <dc:creator>Vílchez Rienda, José Dámaso</dc:creator>
4. <dc:creator>Girón González, María Dolores</dc:creator>
5. <dc:creator>Cabrera, Elena</dc:creator>
6. <dc:creator>Campos, Nefertiti</dc:creator>
7. <dc:creator>Manzano, Manuel</dc:creator>
8. <dc:creator>Rueda Cabrera, Ricardo</dc:creator>
9. <dc:creator>López-Pedrosa, José M.</dc:creator>
10. <dc:subject>Neurites</dc:subject>
11. <dc:subject>Neuronal differentiation</dc:subject>
12. <dc:subject>Neurons</dc:subject>
13. <dc:subject>Protein synthesis</dc:subject>
14. <dc:subject>Neuronal plasticity</dc:subject>
15. <dc:subject>Cell differentiation</dc:subject>
16. <dc:subject>Muscle differentiation</dc:subject>
17. <dc:subject>Phosphorylation</dc:subject>
18. <dc:description>β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.</dc:description>
19. <dc:description>This project has been funded by Abbott Nutrition R&D.</dc:description>
20. <dc:date>2015-09-09T09:50:55Z</dc:date>
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  4. <dc:creator>Cabrera, Elena</dc:creator>
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