title: Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy.
abstract: Autophagy has recently emerged as an important cellular process for the maintenance of skeletal muscle health and function. Excessive autophagy can trigger muscle catabolism, leading to atrophy. In contrast, reduced autophagic flux is a characteristic of several muscle diseases, including Duchenne muscular dystrophy, the most common and severe inherited muscle disorder. Recent evidence demonstrates that enhanced reactive oxygen species (ROS) production by CYBB/NOX2 impairs autophagy in muscles from the dmd/mdx mouse, a genetic model of Duchenne muscular dystrophy. Statins decrease CYBB/NOX2 expression and activity and stimulate autophagy in skeletal muscle. Therefore, we treated dmd/mdx mice with simvastatin and showed decreased CYBB/NOX2-mediated oxidative stress and enhanced autophagy induction. This was accompanied by reduced muscle damage, inflammation and fibrosis, and increased muscle force production. Our data suggest that increased autophagy may be a potential mechanism by which simvastatin improves skeletal muscle health and function in muscular dystrophy.
authors.affiliation: a Department of Physiology and Biophysics , University of Washington , Seattle , WA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Whitehead
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D008954:Models, Biological; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D019821:Simvastatin; D019255:NADPH Oxidases
keywords: CYBB/NOX2; autophagy; fibrosis; inflammation; muscle function; muscular dystrophy; oxidative stress; simvastatin