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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/37312

Title: β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells
Authors: Salto González, Rafael
Vílchez Rienda, José Dámaso
Girón González, María Dolores
Cabrera, Elena
Campos, Nefertiti
Manzano, Manuel
Rueda Cabrera, Ricardo
López-Pedrosa, José M.
Issue Date: 2015
Abstract: 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.
Sponsorship: This project has been funded by Abbott Nutrition R&D.
Publisher: Public Library of Science (PLOS)
Keywords: Neurites
Neuronal differentiation
Neurons
Protein synthesis
Neuronal plasticity
Cell differentiation
Muscle differentiation
Phosphorylation
URI: http://hdl.handle.net/10481/37312
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: 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]
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