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Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway
AIM: To study the effects of exercise on lysosomal functions. METHODS: Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00‐17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515701/ https://www.ncbi.nlm.nih.gov/pubmed/30864262 http://dx.doi.org/10.1111/cns.13114 |
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author | Huang, Jun Wang, Xue Zhu, Yi Li, Zhe Zhu, Yu‐Ting Wu, Jun‐Chao Qin, Zheng‐Hong Xiang, Min Lin, Fang |
author_facet | Huang, Jun Wang, Xue Zhu, Yi Li, Zhe Zhu, Yu‐Ting Wu, Jun‐Chao Qin, Zheng‐Hong Xiang, Min Lin, Fang |
author_sort | Huang, Jun |
collection | PubMed |
description | AIM: To study the effects of exercise on lysosomal functions. METHODS: Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00‐17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluorescence histochemistry. The transmission electron microscopic examination was used to show the structure of lysosome and mitochondria. RESULTS: Exercise promoted the nuclear translocation of TFEB in the cortex which upregulated the transcription of genes associated with autophagy and lysosome. Exercise directly activated autophagy/lysosome system via up‐regulating of AMPK‐SIRT1 signaling. The SIRT1 inhibitor EX527 decreased TFEB regulated gene transcription but had little effect on the nuclear translocation of TFEB. In addition, long‐term exercise showed more significant effects on activation of lysosomes biogenesis compared with the short‐term exercise and trehalose, a classical autophagy activator in the mTOR‐independent pathway. CONCLUSION: Running exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway. |
format | Online Article Text |
id | pubmed-6515701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65157012019-06-26 Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway Huang, Jun Wang, Xue Zhu, Yi Li, Zhe Zhu, Yu‐Ting Wu, Jun‐Chao Qin, Zheng‐Hong Xiang, Min Lin, Fang CNS Neurosci Ther Original Articles AIM: To study the effects of exercise on lysosomal functions. METHODS: Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00‐17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluorescence histochemistry. The transmission electron microscopic examination was used to show the structure of lysosome and mitochondria. RESULTS: Exercise promoted the nuclear translocation of TFEB in the cortex which upregulated the transcription of genes associated with autophagy and lysosome. Exercise directly activated autophagy/lysosome system via up‐regulating of AMPK‐SIRT1 signaling. The SIRT1 inhibitor EX527 decreased TFEB regulated gene transcription but had little effect on the nuclear translocation of TFEB. In addition, long‐term exercise showed more significant effects on activation of lysosomes biogenesis compared with the short‐term exercise and trehalose, a classical autophagy activator in the mTOR‐independent pathway. CONCLUSION: Running exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway. John Wiley and Sons Inc. 2019-03-12 /pmc/articles/PMC6515701/ /pubmed/30864262 http://dx.doi.org/10.1111/cns.13114 Text en © 2019 The Authors CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Huang, Jun Wang, Xue Zhu, Yi Li, Zhe Zhu, Yu‐Ting Wu, Jun‐Chao Qin, Zheng‐Hong Xiang, Min Lin, Fang Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title | Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title_full | Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title_fullStr | Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title_full_unstemmed | Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title_short | Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway |
title_sort | exercise activates lysosomal function in the brain through ampk‐sirt1‐tfeb pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515701/ https://www.ncbi.nlm.nih.gov/pubmed/30864262 http://dx.doi.org/10.1111/cns.13114 |
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