HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/R704    most recent 00031.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Dudley, R. W. R. Articles by Petrof, B. J. Search for Related Content PubMed PubMed Citation Articles by Dudley, R. W. R. Articles by Petrof, B. J.

INFLAMMATION AND CYTOKINES

Dynamic responses of the glutathione system to acute oxidative stress in dystrophic mouse (mdx) muscles

¹Meakins-Christie Laboratories, McGill University, and Respiratory Division of the McGill University Health Center, Montreal, Quebec; ²Department of Nutrition and Montreal Heart Institute, University of Montreal, Montreal, Quebec; and ³Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada

Submitted 12 January 2006 ; accepted in final form 5 April 2006

The precise mechanisms underlying skeletal muscle damage in Duchenne muscular dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation, with subsequent reperfusion during rest, has been documented. Therefore, one possibility is the presence of increased oxidative stress. We applied a model of acute hindlimb ischemia/reperfusion (I/R) in mdx mice (genetic homolog of DMD) to evaluate dynamic in vivo responses of dystrophic muscles to this form of oxidative stress. Before the application of I/R, mdx muscles showed: 1) decreased levels of total glutathione (GSH) with an increased oxidized (GSSG)-to-reduced (GSH) glutathione ratio; 2) greater activity of the GSH-metabolizing enzymes glutathione peroxidase (GPx) and glutathione reductase; and 3) lower activity levels of NADP-linked isocitrate dehydrogenase (ICDH) and aconitase, two metabolic enzymes that are sensitive to inactivation by oxidative stress and also implicated in GSH regeneration. Interestingly, nondystrophic muscles subjected to I/R exhibited similar changes in total glutathione, GSSG/GSH, GPx, ICDH, and aconitase. In contrast, all of the above remained stable in mdx muscles subjected to I/R. Taken together, these results suggest that mdx muscles are chronically subjected to increased oxidative stress, leading to adaptive changes that attempt to protect (although only in part) the dystrophic muscles from acute I/R-induced oxidative stress. In addition, mdx muscles show significant impairment of the redox-sensitive metabolic enzymes ICDH and aconitase, which may further contribute to contractile dysfunction in dystrophic muscles.

reduced glutathione; glutathione reductase; Duchenne muscular dystrophy

This article has been cited by other articles:

				T. F. Reardon and D. G. Allen Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance Exp Physiol, June 1, 2009; 94(6): 720 - 730. [Abstract] [Full Text] [PDF]