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Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2
Hypoxanthine (Hx), an intermediate metabolite of the purine metabolism pathway which is dramatically increased in blood and skeletal muscle during muscle contraction and metabolism, is characterized as a marker of exercise exhaustion. However, the physiological effects of Hx on skeletal muscle remai...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966526/ https://www.ncbi.nlm.nih.gov/pubmed/33746782 http://dx.doi.org/10.3389/fphys.2021.647743 |
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author | Yin, Cong Ma, Zewei Li, Fan Duan, Chen Yuan, Yexian Zhu, Canjun Wang, Lina Zhu, Xiaotong Wang, Songbo Gao, Ping Shu, Gang Zhang, Huihua Jiang, Qingyan |
author_facet | Yin, Cong Ma, Zewei Li, Fan Duan, Chen Yuan, Yexian Zhu, Canjun Wang, Lina Zhu, Xiaotong Wang, Songbo Gao, Ping Shu, Gang Zhang, Huihua Jiang, Qingyan |
author_sort | Yin, Cong |
collection | PubMed |
description | Hypoxanthine (Hx), an intermediate metabolite of the purine metabolism pathway which is dramatically increased in blood and skeletal muscle during muscle contraction and metabolism, is characterized as a marker of exercise exhaustion. However, the physiological effects of Hx on skeletal muscle remain unknown. Herein, we demonstrate that chronic treatment with Hx through dietary supplementation resulted in skeletal muscle fatigue and impaired the exercise performance of mice without affecting their growth and skeletal muscle development. Hx increased the uncoupling protein 2 (UCP2) expression in the skeletal muscle, which led to decreased energy substrate storage and enhanced glycolysis. These effects could also be verified in acute treatment with Hx through intraperitoneal injection. In addition, muscular specifically knockout of UCP2 through intra-muscle tissue injection of adenovirus-associated virus reversed the effects of Hx. In conclusion, we identified a novel role of Hx in the skeletal muscular fatigue mediated by UCP2-dependent mitochondrial uncoupling. This finding may shed light on the pathological mechanism of clinical muscle dysfunctions due to abnormal metabolism, such as muscle fatigue and weakness. |
format | Online Article Text |
id | pubmed-7966526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79665262021-03-18 Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 Yin, Cong Ma, Zewei Li, Fan Duan, Chen Yuan, Yexian Zhu, Canjun Wang, Lina Zhu, Xiaotong Wang, Songbo Gao, Ping Shu, Gang Zhang, Huihua Jiang, Qingyan Front Physiol Physiology Hypoxanthine (Hx), an intermediate metabolite of the purine metabolism pathway which is dramatically increased in blood and skeletal muscle during muscle contraction and metabolism, is characterized as a marker of exercise exhaustion. However, the physiological effects of Hx on skeletal muscle remain unknown. Herein, we demonstrate that chronic treatment with Hx through dietary supplementation resulted in skeletal muscle fatigue and impaired the exercise performance of mice without affecting their growth and skeletal muscle development. Hx increased the uncoupling protein 2 (UCP2) expression in the skeletal muscle, which led to decreased energy substrate storage and enhanced glycolysis. These effects could also be verified in acute treatment with Hx through intraperitoneal injection. In addition, muscular specifically knockout of UCP2 through intra-muscle tissue injection of adenovirus-associated virus reversed the effects of Hx. In conclusion, we identified a novel role of Hx in the skeletal muscular fatigue mediated by UCP2-dependent mitochondrial uncoupling. This finding may shed light on the pathological mechanism of clinical muscle dysfunctions due to abnormal metabolism, such as muscle fatigue and weakness. Frontiers Media S.A. 2021-03-03 /pmc/articles/PMC7966526/ /pubmed/33746782 http://dx.doi.org/10.3389/fphys.2021.647743 Text en Copyright © 2021 Yin, Ma, Li, Duan, Yuan, Zhu, Wang, Zhu, Wang, Gao, Shu, Zhang and Jiang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Yin, Cong Ma, Zewei Li, Fan Duan, Chen Yuan, Yexian Zhu, Canjun Wang, Lina Zhu, Xiaotong Wang, Songbo Gao, Ping Shu, Gang Zhang, Huihua Jiang, Qingyan Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title | Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title_full | Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title_fullStr | Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title_full_unstemmed | Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title_short | Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2 |
title_sort | hypoxanthine induces muscular atp depletion and fatigue via ucp2 |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966526/ https://www.ncbi.nlm.nih.gov/pubmed/33746782 http://dx.doi.org/10.3389/fphys.2021.647743 |
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