McArdle disease (MD) is a metabolic myopathy due to myophosphorylase deficiency, which leads to a severe limitation in the rate of adenosine triphosphate (ATP) resynthesis. Compensatory flux through the myoadenylate deaminase > > xanthine oxidase pathway should result in higher oxidative stress in skeletal muscle; however, oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidant response cascade in MD patients have not yet been examined. We show that MD patients have elevated muscle protein carbonyls and 4-hydroxynonenal (4-HNE) in comparison with healthy, age and activity matched controls (P < 0.05). Nuclear abundance of Nrf2 and Nrf2-antioxidant response element (ARE) binding was also higher in MD patients compared with controls (P < 0.05). The expressions of Nrf2 target genes were also higher in MD patients vs. controls. These observations suggest that MD patients experience elevated levels of oxidative stress, and that the Nrf2-mediated antioxidant response cascade is up-regulated in skeletal muscle to compensate.
Keywords: ADP; AMP; ARE; ATP; GCLC; GCLM; GPX; HMOX1; Keap1; Kelch-like ECH-associated protein 1; MD; McArdle disease; NAD(P)H quinone oxidoreductase 1; NQO1; Nrf2; Nuclear factor erythroid 2-related factor 2; Oxidative stress; PYGM; TXNRD; adenosine diphosphate; adenosine monophosphate; adenosine triphosphate; antioxidant response element; glutathione peroxidase; heme oxygenase 1; muscle glycogen phosphorylase; nuclear factor erythroid 2-related factor 2; thioredoxin reductase; γ-glutamylcysteine ligase catalytic subunit; γ-glutamylcysteine ligase regulatory subunit.
© 2013.