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Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load
Phosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876046/ https://www.ncbi.nlm.nih.gov/pubmed/33568757 http://dx.doi.org/10.1038/s41598-021-83098-z |
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author | Kuramoto, Naoki Nomura, Kazuhiro Kohno, Daisuke Kitamura, Tadahiro Karsenty, Gerard Hosooka, Tetsuya Ogawa, Wataru |
author_facet | Kuramoto, Naoki Nomura, Kazuhiro Kohno, Daisuke Kitamura, Tadahiro Karsenty, Gerard Hosooka, Tetsuya Ogawa, Wataru |
author_sort | Kuramoto, Naoki |
collection | PubMed |
description | Phosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β(2)-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β(2)-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β(2)-AR. |
format | Online Article Text |
id | pubmed-7876046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78760462021-02-11 Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load Kuramoto, Naoki Nomura, Kazuhiro Kohno, Daisuke Kitamura, Tadahiro Karsenty, Gerard Hosooka, Tetsuya Ogawa, Wataru Sci Rep Article Phosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β(2)-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β(2)-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β(2)-AR. Nature Publishing Group UK 2021-02-10 /pmc/articles/PMC7876046/ /pubmed/33568757 http://dx.doi.org/10.1038/s41598-021-83098-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kuramoto, Naoki Nomura, Kazuhiro Kohno, Daisuke Kitamura, Tadahiro Karsenty, Gerard Hosooka, Tetsuya Ogawa, Wataru Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title | Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title_full | Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title_fullStr | Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title_full_unstemmed | Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title_short | Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load |
title_sort | role of pdk1 in skeletal muscle hypertrophy induced by mechanical load |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876046/ https://www.ncbi.nlm.nih.gov/pubmed/33568757 http://dx.doi.org/10.1038/s41598-021-83098-z |
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