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: 586/7/2003    most recent jphysiol.2007.148338v1 Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Whitehead, N. P. Articles by Allen, D. G. Search for Related Content PubMed PubMed Citation Articles by Whitehead, N. P. Articles by Allen, D. G. Related Collections Skeletal Muscle and Exercise Related Article

¹ Bosch Institute, School of Medical Sciences, University of Sydney F13, Sydney, NSW 2006, Australia

Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by a mutation in the gene encoding dystrophin, a protein linking the cytoskeleton to the extracellular matrix. In this study we investigated whether the antioxidant N-acetylcysteine (NAC) provided protection against dystrophic muscle damage in the mdx mouse, an animal model of DMD. In isolated mdx muscles, NAC prevented the increased membrane permeability and reduced the force deficit associated with stretch-induced muscle damage. Three-week-old mdx mice were treated with NAC in the drinking water for 6 weeks. Dihydroethidium staining showed that NAC treatment reduced the concentration of reactive oxygen species (ROS) in mdx muscles. This was accompanied by a significant decrease in centrally nucleated fibres in muscles from NAC-treated mdx mice. Immunoblotting showed that NAC treatment decreased the nuclear protein expression of NF-B, a transcription factor involved in pro-inflammatory cytokine expression. Finally, we show that NAC treatment reduced caveolin-3 protein levels and increased the sarcolemmal expression of β-dystroglycan and the dystrophin homologue, utrophin. Taken together, our findings suggest that ROS play an important role in the dystrophic pathogenesis, both in terms of activating damage pathways and in regulating the expression of some dystrophin-associated membrane proteins. These results offer the prospect that antioxidants such as NAC could have therapeutic potential for DMD patients.

(Received 15 November 2007; accepted after revision 4 February 2008; first published online 7 February 2008)
Corresponding author N. P. Whitehead: Bosch Institute, School of Medical Sciences, University of Sydney F13, Sydney, NSW 2006, Australia.  Email: nickw{at}physiol.usyd.edu.au

Related Article

Between channels and tears: aim at ROS to save the membrane of dystrophic fibres

Carlo Reggiani
J. Physiol. 2008 586: 1779. [Full Text] [PDF]

This article has been cited by other articles:

				B. Blaauw, C. Mammucari, L. Toniolo, L. Agatea, R. Abraham, M. Sandri, C. Reggiani, and S. Schiaffino Akt activation prevents the force drop induced by eccentric contractions in dystrophin-deficient skeletal muscle Hum. Mol. Genet., December 1, 2008; 17(23): 3686 - 3696. [Abstract] [Full Text] [PDF]

				O. L. Gervasio, N. P. Whitehead, E. W. Yeung, W. D. Phillips, and D. G. Allen TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy J. Cell Sci., July 1, 2008; 121(13): 2246 - 2255. [Abstract] [Full Text] [PDF]

				C. Reggiani Between channels and tears: aim at ROS to save the membrane of dystrophic fibres J. Physiol., April 1, 2008; 586(7): 1779 - 1779. [Full Text] [PDF]