Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

Abstract 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...

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Autores principales:	Naoki Kuramoto, Kazuhiro Nomura, Daisuke Kohno, Tadahiro Kitamura, Gerard Karsenty, Tetsuya Hosooka, Wataru Ogawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c29e639e6c14990af1ddb5203233689
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spelling	oai:doaj.org-article:0c29e639e6c14990af1ddb52032336892021-12-02T13:30:34ZRole of PDK1 in skeletal muscle hypertrophy induced by mechanical load10.1038/s41598-021-83098-z2045-2322https://doaj.org/article/0c29e639e6c14990af1ddb52032336892021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83098-zhttps://doaj.org/toc/2045-2322Abstract 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 β2-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 β2-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 β2-AR.Naoki KuramotoKazuhiro NomuraDaisuke KohnoTadahiro KitamuraGerard KarsentyTetsuya HosookaWataru OgawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoki Kuramoto Kazuhiro Nomura Daisuke Kohno Tadahiro Kitamura Gerard Karsenty Tetsuya Hosooka Wataru Ogawa Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load
description	Abstract 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 β2-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 β2-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 β2-AR.
format	article
author	Naoki Kuramoto Kazuhiro Nomura Daisuke Kohno Tadahiro Kitamura Gerard Karsenty Tetsuya Hosooka Wataru Ogawa
author_facet	Naoki Kuramoto Kazuhiro Nomura Daisuke Kohno Tadahiro Kitamura Gerard Karsenty Tetsuya Hosooka Wataru Ogawa
author_sort	Naoki Kuramoto
title	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_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_sort	role of pdk1 in skeletal muscle hypertrophy induced by mechanical load
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c29e639e6c14990af1ddb5203233689
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Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

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