Mitophagy protects against statin-mediated skeletal muscle toxicity.
Animals
Caspase 3
/ metabolism
Cell Line
Cytochromes c
/ metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ pharmacology
L-Lactate Dehydrogenase
/ metabolism
Mice, Knockout
Mitophagy
/ drug effects
Muscle, Skeletal
/ cytology
Myoblasts
/ cytology
RNA Interference
Sequestosome-1 Protein
/ genetics
Simvastatin
/ pharmacology
Ubiquitin-Protein Ligases
/ genetics
mitochondria
myopathy
simvastatin
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
pubmed:
1
8
2019
medline:
9
6
2020
entrez:
1
8
2019
Statut:
ppublish
Résumé
The deleterious effects of statins on skeletal muscle are well known, but the mechanism associated with these effects remains unresolved. Statins are associated with mitochondrial damage, which may contribute to muscle myopathy. Here we demonstrate that simvastatin induces mitophagy in skeletal muscle cells and hypothesized that attenuating this process by silencing the mitophagy adapter p62/sequestosome-1 (SQSTM1) might mitigate myotoxicity. Surprisingly, silencing p62/SQSTM1 in differentiated C2C12 muscle cells exacerbated rather than attenuated myotoxicity. This inhibition of mitophagy in the face of statin challenge correlated with increased release of cytochrome
Identifiants
pubmed: 31365836
doi: 10.1096/fj.201900807RR
pmc: PMC6902735
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Sequestosome-1 Protein
0
Sqstm1 protein, mouse
0
Cytochromes c
9007-43-6
Simvastatin
AGG2FN16EV
L-Lactate Dehydrogenase
EC 1.1.1.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
parkin protein
EC 2.3.2.27
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11857-11869Références
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