Higher oxidative stress in skeletal muscle of McArdle disease patients

Jan J Kaczor; Holly A Robertshaw; Mark A Tarnopolsky

doi:10.1016/j.ymgmr.2017.05.009

Higher oxidative stress in skeletal muscle of McArdle disease patients

Mol Genet Metab Rep. 2017 Jun 9:12:69-75. doi: 10.1016/j.ymgmr.2017.05.009. eCollection 2017 Sep.

Authors

Jan J Kaczor^{1

2}, Holly A Robertshaw¹, Mark A Tarnopolsky^{1

3}

Affiliations

¹ Department of Pediatrics, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
² Department of Neurobiology of Muscle, Gdansk University of Physical Education and Sport, Gdansk, Poland.
³ Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.

Abstract

McArdle disease (MCD) is an autosomal recessive condition resulting from skeletal muscle glycogen phosphorylase deficiency. The resultant block in glycogenolysis leads to an increased flux through the xanthine oxidase pathway (myogenic hyperuricemia) and could lead to an increase in oxidative stress. We examined markers of oxidative stress (8-isoprostane and protein carbonyls), NAD(P)H-oxidase, xanthine oxidase and antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activity in skeletal muscle of MCD patients (N = 12) and controls (N = 12). Eight-isoprostanes and protein carbonyls were higher in MCD patients as compared to controls (p < 0.05). There was a compensatory up-regulation of catalase protein content and activity (p < 0.05), mitochondrial superoxide dismutase (MnSOD) protein content (p < 0.01) and activity (p < 0.05) in MCD patients, yet this increase was not sufficient to protect the muscle against elevated oxidative damage. These results suggest that oxidative stress in McArdle patients occurs and future studies should evaluate a potential role for oxidative stress contributing to acute pathology (rhabdomyolysis) and possibly later onset fixed myopathy.

Keywords: Enzyme activity; McArdle disease; Oxidative stress; Skeletal muscle.