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Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

BACKGROUND: Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autop...

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Autores principales: Spaulding, HR, Ballmann, C, Quindry, JC, Hudson, MB, Selsby, JT
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790947/
https://www.ncbi.nlm.nih.gov/pubmed/31656622
http://dx.doi.org/10.1177/2048004019879581
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author Spaulding, HR
Ballmann, C
Quindry, JC
Hudson, MB
Selsby, JT
author_facet Spaulding, HR
Ballmann, C
Quindry, JC
Hudson, MB
Selsby, JT
author_sort Spaulding, HR
collection PubMed
description BACKGROUND: Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. METHODS: Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. RESULTS: Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn(±) mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. CONCLUSION: Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.
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spelling pubmed-67909472019-10-25 Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models Spaulding, HR Ballmann, C Quindry, JC Hudson, MB Selsby, JT JRSM Cardiovasc Dis Research Paper BACKGROUND: Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. METHODS: Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. RESULTS: Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn(±) mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. CONCLUSION: Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction. SAGE Publications 2019-09-29 /pmc/articles/PMC6790947/ /pubmed/31656622 http://dx.doi.org/10.1177/2048004019879581 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Paper
Spaulding, HR
Ballmann, C
Quindry, JC
Hudson, MB
Selsby, JT
Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title_full Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title_fullStr Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title_full_unstemmed Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title_short Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
title_sort autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790947/
https://www.ncbi.nlm.nih.gov/pubmed/31656622
http://dx.doi.org/10.1177/2048004019879581
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