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Indices of autophagy are unaltered by quercetin consumption in hearts of Mdx/Utrn +/− mice
Author(s) -
Quindry John C,
Quindry Tiffany S,
Ballmann Christopher G,
Selsby Joshua T
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.688.9
Subject(s) - atg5 , autophagy , quercetin , duchenne muscular dystrophy , medicine , cardiomyopathy , endocrinology , mdx mouse , dystrophin , heart failure , biology , biochemistry , apoptosis , antioxidant
A significant percentage of Duchenne muscular dystrophy (DMD) is associated with progressive cardiac damage and heart failure. The extent to which autophagy is altered in the dystrophic myocardium with advanced disease is unknown. DMD countermeasures, and prevention of resultant cardiomyopathy, may correct disease‐related autophagic dysfunction. Using mouse models, our lab has demonstrated previously that long‐term consumption of the flavonol quercetin benefits physiologic, biochemical, and histological outcomes in dystrophic hearts. The purpose of this investigation was to determine the extent to which 1) autophagy is dysregulated in dystrophic hearts with advanced disease, and 2) whether indices of autophagic dysfunction are corrected by oral quercetin administration. Hearts harvested from untreated 10‐month old C57, Mdx/Utro+/‐ (heterozygous for a utrophin knockout), and Mdx/Utro+/− treated with a 0.2% quercetin enriched diet from 2–10 months of age. In these hearts we have previously reported widespread dystrophic injury that was largely corrected by the quercetin intervention. Using a western blot approach, dependent measures included relative abundance of key autophagic markers including Atg5, Atg7, beclin‐1, LC3II/I, and p62. Results indicate that Atg5 (p=0.779), Atg7 (p=0.895), beclin‐1 (p=0.251), and p62 (p=0.064) were similar between groups. The LC3II/I ratio was similarly unaffected by 8 months of quercetin treatment, although a strain‐dependent effect (p=0.038) was observed with Mdx/Utrn +/− Q and Mdx/Utrn +/− being 44% and 56% lower than C57, respectively. Based on these preliminary findings, disease‐related injury is independent of changes in autophagic signaling. Moreover, quercetin‐mediated protection appears to be unrealated to alterations to the autophagic process. Additional metrics of autophagic flux and examination using other animal models are needed to confirm the current findings. Support or Funding Information Funded by: Duchenne Alliance and its member foundations