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Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis
AIMS: Insulin and glucocorticoids play crucial roles in skeletal muscle protein turnover. Fast-twitch glycolytic fibres are more susceptible to atrophy than slow-twitch oxidative fibres. Based on accumulating evidence, hydrogen sulfide (H(2)S) is a physiological mediator of this process. The regulat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476024/ https://www.ncbi.nlm.nih.gov/pubmed/31089421 http://dx.doi.org/10.1155/2019/9752698 |
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author | Wang, Ruxia Li, Kelin Wang, Hui Jiao, Hongchao Wang, Xiaojuan Zhao, Jingpeng Lin, Hai |
author_facet | Wang, Ruxia Li, Kelin Wang, Hui Jiao, Hongchao Wang, Xiaojuan Zhao, Jingpeng Lin, Hai |
author_sort | Wang, Ruxia |
collection | PubMed |
description | AIMS: Insulin and glucocorticoids play crucial roles in skeletal muscle protein turnover. Fast-twitch glycolytic fibres are more susceptible to atrophy than slow-twitch oxidative fibres. Based on accumulating evidence, hydrogen sulfide (H(2)S) is a physiological mediator of this process. The regulatory effect of H(2)S on protein synthesis in fast-twitch fibres was evaluated. RESULTS: A NaHS (sodium hydrosulfide) injection simultaneously increased the diameter of M. pectoralis major (i.e., fast-twitch glycolytic fibres) and activated the mammalian target of the rapamycin (mTOR)/p70S6 kinase (p70S6K) pathway. Dexamethasone (DEX) inhibited protein synthesis, downregulated mTOR and p70S6K phosphorylation, and suppressed the expression of the cystathionine γ-lyase (CSE) protein in myoblasts. The precursor of H(2)S, L-cysteine, completely abolished the inhibitory effects of DEX. The CSE inhibitor DL-propargylglycine (PAG) completely abrogated the effects of RU486 on blocking the suppressive effects of DEX. The H(2)S donor NaHS increased the H(2)S concentrations and abrogated the inhibitory effects of DEX on protein synthesis. Insulin increased protein synthesis and upregulated CSE expression. However, PAG abrogated the stimulatory effects of insulin on protein synthesis and the activity of the mTOR/p70S6K pathway. INNOVATION: These results demonstrated that CSE/H(2)S regulated protein synthesis in fast-twitch muscle fibres, and glucocorticoids and insulin regulated protein synthesis in an endogenous CSE/H(2)S system-dependent manner. CONCLUSIONS: The results from the present study suggest that the endogenous CSE/H(2)S system regulates fast-twitch glycolytic muscle degeneration and regeneration. |
format | Online Article Text |
id | pubmed-6476024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-64760242019-05-14 Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis Wang, Ruxia Li, Kelin Wang, Hui Jiao, Hongchao Wang, Xiaojuan Zhao, Jingpeng Lin, Hai Oxid Med Cell Longev Research Article AIMS: Insulin and glucocorticoids play crucial roles in skeletal muscle protein turnover. Fast-twitch glycolytic fibres are more susceptible to atrophy than slow-twitch oxidative fibres. Based on accumulating evidence, hydrogen sulfide (H(2)S) is a physiological mediator of this process. The regulatory effect of H(2)S on protein synthesis in fast-twitch fibres was evaluated. RESULTS: A NaHS (sodium hydrosulfide) injection simultaneously increased the diameter of M. pectoralis major (i.e., fast-twitch glycolytic fibres) and activated the mammalian target of the rapamycin (mTOR)/p70S6 kinase (p70S6K) pathway. Dexamethasone (DEX) inhibited protein synthesis, downregulated mTOR and p70S6K phosphorylation, and suppressed the expression of the cystathionine γ-lyase (CSE) protein in myoblasts. The precursor of H(2)S, L-cysteine, completely abolished the inhibitory effects of DEX. The CSE inhibitor DL-propargylglycine (PAG) completely abrogated the effects of RU486 on blocking the suppressive effects of DEX. The H(2)S donor NaHS increased the H(2)S concentrations and abrogated the inhibitory effects of DEX on protein synthesis. Insulin increased protein synthesis and upregulated CSE expression. However, PAG abrogated the stimulatory effects of insulin on protein synthesis and the activity of the mTOR/p70S6K pathway. INNOVATION: These results demonstrated that CSE/H(2)S regulated protein synthesis in fast-twitch muscle fibres, and glucocorticoids and insulin regulated protein synthesis in an endogenous CSE/H(2)S system-dependent manner. CONCLUSIONS: The results from the present study suggest that the endogenous CSE/H(2)S system regulates fast-twitch glycolytic muscle degeneration and regeneration. Hindawi 2019-04-07 /pmc/articles/PMC6476024/ /pubmed/31089421 http://dx.doi.org/10.1155/2019/9752698 Text en Copyright © 2019 Ruxia Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Ruxia Li, Kelin Wang, Hui Jiao, Hongchao Wang, Xiaojuan Zhao, Jingpeng Lin, Hai Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title | Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title_full | Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title_fullStr | Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title_full_unstemmed | Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title_short | Endogenous CSE/Hydrogen Sulfide System Regulates the Effects of Glucocorticoids and Insulin on Muscle Protein Synthesis |
title_sort | endogenous cse/hydrogen sulfide system regulates the effects of glucocorticoids and insulin on muscle protein synthesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476024/ https://www.ncbi.nlm.nih.gov/pubmed/31089421 http://dx.doi.org/10.1155/2019/9752698 |
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