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Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394462/ https://www.ncbi.nlm.nih.gov/pubmed/28417963 http://dx.doi.org/10.1038/srep46369 |
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author | Mandai, Shintaro Furukawa, Susumu Kodaka, Manami Hata, Yutaka Mori, Takayasu Nomura, Naohiro Ando, Fumiaki Mori, Yutaro Takahashi, Daiei Yoshizaki, Yuki Kasagi, Yuri Arai, Yohei Sasaki, Emi Yoshida, Sayaka Furuichi, Yasuro Fujii, Nobuharu L. Sohara, Eisei Rai, Tatemitsu Uchida, Shinichi |
author_facet | Mandai, Shintaro Furukawa, Susumu Kodaka, Manami Hata, Yutaka Mori, Takayasu Nomura, Naohiro Ando, Fumiaki Mori, Yutaro Takahashi, Daiei Yoshizaki, Yuki Kasagi, Yuri Arai, Yohei Sasaki, Emi Yoshida, Sayaka Furuichi, Yasuro Fujii, Nobuharu L. Sohara, Eisei Rai, Tatemitsu Uchida, Shinichi |
author_sort | Mandai, Shintaro |
collection | PubMed |
description | Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics. NKCC1 protein levels increased during C2C12 murine skeletal myoblast differentiation, similarly to those of the myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly suppressed myoblast fusion into myotubes and the expression of myogenin and MHC. Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse skeletal muscles after 6 weeks’ voluntary wheel running. Immunofluorescence analyses of myofiber cross-sections revealed more large myofibers after exercise, but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10 mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart failure may be attributable to treatment with loop diuretics. |
format | Online Article Text |
id | pubmed-5394462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53944622017-04-20 Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy Mandai, Shintaro Furukawa, Susumu Kodaka, Manami Hata, Yutaka Mori, Takayasu Nomura, Naohiro Ando, Fumiaki Mori, Yutaro Takahashi, Daiei Yoshizaki, Yuki Kasagi, Yuri Arai, Yohei Sasaki, Emi Yoshida, Sayaka Furuichi, Yasuro Fujii, Nobuharu L. Sohara, Eisei Rai, Tatemitsu Uchida, Shinichi Sci Rep Article Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(−) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics. NKCC1 protein levels increased during C2C12 murine skeletal myoblast differentiation, similarly to those of the myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly suppressed myoblast fusion into myotubes and the expression of myogenin and MHC. Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse skeletal muscles after 6 weeks’ voluntary wheel running. Immunofluorescence analyses of myofiber cross-sections revealed more large myofibers after exercise, but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10 mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart failure may be attributable to treatment with loop diuretics. Nature Publishing Group 2017-04-18 /pmc/articles/PMC5394462/ /pubmed/28417963 http://dx.doi.org/10.1038/srep46369 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Mandai, Shintaro Furukawa, Susumu Kodaka, Manami Hata, Yutaka Mori, Takayasu Nomura, Naohiro Ando, Fumiaki Mori, Yutaro Takahashi, Daiei Yoshizaki, Yuki Kasagi, Yuri Arai, Yohei Sasaki, Emi Yoshida, Sayaka Furuichi, Yasuro Fujii, Nobuharu L. Sohara, Eisei Rai, Tatemitsu Uchida, Shinichi Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title | Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title_full | Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title_fullStr | Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title_full_unstemmed | Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title_short | Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
title_sort | loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394462/ https://www.ncbi.nlm.nih.gov/pubmed/28417963 http://dx.doi.org/10.1038/srep46369 |
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