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Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes

We previously determined that different vitamin D metabolites can have opposite effects on C2C12 myotubes, depending on the sites of hydroxylation or doses. Specifically, 25(OH)D(3) (25VD) has an anti-atrophic activity, 1,25(OH)(2)D(3) induces atrophy, and 24,25(OH)(2)D(3) is anti-atrophic at low co...

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Autores principales: Teixeira, Maraiza Alves, De Feudis, Marilisa, Reano, Simone, Raiteri, Tommaso, Scircoli, Andrea, Zaggia, Ivan, Ruga, Sara, Salvadori, Laura, Prodam, Flavia, Marzullo, Paolo, Molinari, Claudio, Corà, Davide, Filigheddu, Nicoletta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950266/
https://www.ncbi.nlm.nih.gov/pubmed/33618332
http://dx.doi.org/10.18632/aging.202669
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author Teixeira, Maraiza Alves
De Feudis, Marilisa
Reano, Simone
Raiteri, Tommaso
Scircoli, Andrea
Zaggia, Ivan
Ruga, Sara
Salvadori, Laura
Prodam, Flavia
Marzullo, Paolo
Molinari, Claudio
Corà, Davide
Filigheddu, Nicoletta
author_facet Teixeira, Maraiza Alves
De Feudis, Marilisa
Reano, Simone
Raiteri, Tommaso
Scircoli, Andrea
Zaggia, Ivan
Ruga, Sara
Salvadori, Laura
Prodam, Flavia
Marzullo, Paolo
Molinari, Claudio
Corà, Davide
Filigheddu, Nicoletta
author_sort Teixeira, Maraiza Alves
collection PubMed
description We previously determined that different vitamin D metabolites can have opposite effects on C2C12 myotubes, depending on the sites of hydroxylation or doses. Specifically, 25(OH)D(3) (25VD) has an anti-atrophic activity, 1,25(OH)(2)D(3) induces atrophy, and 24,25(OH)(2)D(3) is anti-atrophic at low concentrations and atrophic at high concentrations. This study aimed to clarify whether cholecalciferol (VD3) too, the non-hydroxylated upstream metabolite, has a direct effect on muscle cells. Assessing the effects of VD3 treatment on mouse C2C12 skeletal muscle myotubes undergoing atrophy induced by interleukin 6 (IL6), we demonstrated that VD3 has a protective action, preserving C2C12 myotubes size, likely through promoting the differentiation and fusion of residual myoblasts and by modulating the IL6-induced autophagic flux. The lack, in C2C12 myotubes, of the hydroxylase transforming VD3 in the anti-atrophic 25VD metabolite suggests that VD3 may have a direct biological activity on the skeletal muscle. Furthermore, we found that the protective action of VD3 depended on VDR, implying that VD3 too might bind to and activate VDR. However, despite the formation of VDR-RXR heterodimers, VD3 effects do not depend on RXR activity. In conclusion, VD3, in addition to its best-known metabolites, may directly impact on skeletal muscle homeostasis.
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spelling pubmed-79502662021-03-23 Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes Teixeira, Maraiza Alves De Feudis, Marilisa Reano, Simone Raiteri, Tommaso Scircoli, Andrea Zaggia, Ivan Ruga, Sara Salvadori, Laura Prodam, Flavia Marzullo, Paolo Molinari, Claudio Corà, Davide Filigheddu, Nicoletta Aging (Albany NY) Research Paper We previously determined that different vitamin D metabolites can have opposite effects on C2C12 myotubes, depending on the sites of hydroxylation or doses. Specifically, 25(OH)D(3) (25VD) has an anti-atrophic activity, 1,25(OH)(2)D(3) induces atrophy, and 24,25(OH)(2)D(3) is anti-atrophic at low concentrations and atrophic at high concentrations. This study aimed to clarify whether cholecalciferol (VD3) too, the non-hydroxylated upstream metabolite, has a direct effect on muscle cells. Assessing the effects of VD3 treatment on mouse C2C12 skeletal muscle myotubes undergoing atrophy induced by interleukin 6 (IL6), we demonstrated that VD3 has a protective action, preserving C2C12 myotubes size, likely through promoting the differentiation and fusion of residual myoblasts and by modulating the IL6-induced autophagic flux. The lack, in C2C12 myotubes, of the hydroxylase transforming VD3 in the anti-atrophic 25VD metabolite suggests that VD3 may have a direct biological activity on the skeletal muscle. Furthermore, we found that the protective action of VD3 depended on VDR, implying that VD3 too might bind to and activate VDR. However, despite the formation of VDR-RXR heterodimers, VD3 effects do not depend on RXR activity. In conclusion, VD3, in addition to its best-known metabolites, may directly impact on skeletal muscle homeostasis. Impact Journals 2021-02-22 /pmc/articles/PMC7950266/ /pubmed/33618332 http://dx.doi.org/10.18632/aging.202669 Text en Copyright: © 2021 Alves Teixeira et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Teixeira, Maraiza Alves
De Feudis, Marilisa
Reano, Simone
Raiteri, Tommaso
Scircoli, Andrea
Zaggia, Ivan
Ruga, Sara
Salvadori, Laura
Prodam, Flavia
Marzullo, Paolo
Molinari, Claudio
Corà, Davide
Filigheddu, Nicoletta
Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title_full Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title_fullStr Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title_full_unstemmed Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title_short Cholecalciferol (vitamin D(3)) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes
title_sort cholecalciferol (vitamin d(3)) has a direct protective activity against interleukin 6-induced atrophy in c2c12 myotubes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950266/
https://www.ncbi.nlm.nih.gov/pubmed/33618332
http://dx.doi.org/10.18632/aging.202669
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