Oxidative stress and Nrf2 signaling in McArdle disease.

Abstract

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.

• Authors: Yu Kitaoka, Daniel I Ogborn, Mats I Nilsson, Nicholas J Mocellin, Lauren G MacNeil, Mark A Tarnopolsky
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 110 Issue 3 Pg. 297-302 (Nov 2013) ISSN: 1096-7206 [Electronic] United States
• PMID: 23906480 (Publication Type: Journal Article)
• Copyright: © 2013.

Chemical References

• Aldehydes
• Intracellular Signaling Peptides and Proteins
• KEAP1 protein, human
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Uric Acid
• Heme Oxygenase-1
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• Glucosyltransferases
• 4-hydroxy-2-nonenal

Topics

• Aldehydes (metabolism)
• Female
• Gene Expression Regulation
• Glucosyltransferases (metabolism)
• Glycogen Storage Disease Type V (genetics, metabolism)
• Heme Oxygenase-1 (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Kelch-Like ECH-Associated Protein 1
• Male
• Middle Aged
• Mitochondria (metabolism)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (genetics)
• Signal Transduction
• Transcription, Genetic
• Uric Acid (blood)