Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models.
Duchenne muscular dystrophy
heart
mdx
utrophin
Journal
JRSM cardiovascular disease
ISSN: 2048-0040
Titre abrégé: JRSM Cardiovasc Dis
Pays: England
ID NLM: 101598607
Informations de publication
Date de publication:
Historique:
received:
21
02
2019
revised:
13
08
2019
accepted:
27
08
2019
entrez:
29
10
2019
pubmed:
28
10
2019
medline:
28
10
2019
Statut:
epublish
Résumé
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. Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. 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 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.
Sections du résumé
BACKGROUND
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
METHODS
Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts.
RESULTS
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
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 31656622
doi: 10.1177/2048004019879581
pii: 10.1177_2048004019879581
pmc: PMC6790947
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2048004019879581Informations de copyright
© The Author(s) 2019.
Références
Exp Physiol. 2017 Jun 1;102(6):635-649
pubmed: 28192862
PLoS One. 2016 Dec 15;11(12):e0168293
pubmed: 27977770
Am J Physiol Cell Physiol. 2010 Sep;299(3):C706-13
pubmed: 20592245
J Biol Chem. 2000 Mar 31;275(13):9452-60
pubmed: 10734092
Autophagy. 2010 Jul;6(5):600-6
pubmed: 20431347
Basic Res Cardiol. 2011 Nov;106(6):1173-91
pubmed: 21901288
Exp Physiol. 2011 Feb;96(2):194-202
pubmed: 21041317
Circulation. 2011 Aug 2;124(5):582-8
pubmed: 21768542
J Cell Sci. 2013 Dec 1;126(Pt 23):5325-33
pubmed: 24293330
Redox Biol. 2015;4:242-59
pubmed: 25618581
Am J Physiol Heart Circ Physiol. 2017 Jan 1;312(1):H128-H140
pubmed: 27836895
J Neuromuscul Dis. 2017;4(1):17-23
pubmed: 28269790
J Appl Physiol (1985). 2010 Nov;109(5):1492-9
pubmed: 20847128
FASEB J. 2014 May;28(5):2047-61
pubmed: 24500923
Neuromuscul Disord. 2004 Sep;14(8-9):491-6
pubmed: 15336690
Acta Physiol (Oxf). 2018 Feb;222(2):
pubmed: 28834378
Nat Cell Biol. 2013 Jul;15(7):727-8
pubmed: 23817237
Exp Physiol. 2015 Jan;100(1):12-22
pubmed: 25557727
Heart Fail Rev. 2013 Sep;18(5):575-84
pubmed: 23188163
J Physiol. 2016 Oct 15;594(20):6037-6053
pubmed: 27094343
Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H846-55
pubmed: 17012353
Biochim Biophys Acta. 2015 Feb;1852(2):252-61
pubmed: 24882754
J Cell Biol. 2005 Nov 21;171(4):603-14
pubmed: 16286508
Semin Cell Dev Biol. 2017 Apr;64:213-223
pubmed: 27531051
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3710-4
pubmed: 8475120
Aging Cell. 2017 Oct;16(5):976-987
pubmed: 28681509
Nat Commun. 2013;4:2308
pubmed: 23917356
Physiol Rev. 2016 Jan;96(1):253-305
pubmed: 26676145
Nat Commun. 2014 Jul 16;5:4425
pubmed: 25028121
Exp Gerontol. 2011 Jul;46(7):549-59
pubmed: 21377520
Free Radic Biol Med. 2017 Aug;109:108-113
pubmed: 27940349
Cardiovasc Res. 2018 Jan 1;114(1):90-102
pubmed: 29036556
J Physiol. 2012 Nov 1;590(21):5487-502
pubmed: 22907054
J Am Acad Nurse Pract. 2009 May;21(5):241-9
pubmed: 19432907