The involvement of oxidative stress in determining the severity and progress of pathological processes in dystrophin-deficient muscles.
In both forms of muscular dystrophy, the severe Duchenne's muscular dystrophy (DMD) with lifespan shortened to about 20 years and the milder Becker dystrophy (BDM) with normal lifespan, the gene defect is located at chromosome locus Xp21. The location is the same in the experimental model of DMD in the mdx mice. As the result of the gene defect a protein called dystrophin is either not synthesized, or is produced in traces. Although the structure of this protein is rather well established there are still many controversies about the dystrophin function. The most accepted suggestion supposes that it stabilizes sarcolemma in the course of the contraction-relaxation cycle. Solving the problem of dystrophin function is a prerequisite for introduction of an effective therapy. Among the different factors which might be responsible for the appearance and progress of dystrophic changes in muscles there is an excessive action of oxidative stress. In this review data indicating the influence of oxidative stress on the severity of the pathologic processes in dystrophy are discussed. Several pieces of data indicating the action of oxidative damage to different macromolecules in DMD/BDM are presented. Special attention is devoted to the degree of oxidative damage to muscle proteins, the activity of neuronal nitric oxide synthase (nNOS) and their involvement in defining the severity of the dystrophic processes. It is indicated that the severity of the morbid process is related to the degree of oxidative damage to muscle proteins and the decrease of the nNOS activity in muscles. Estimation of the degree of the destructive action of oxidative stress in muscular dystrophy may be a useful marker facilitating introduction of an effective antioxidant therapy and regulation of nNOS activity.
Niebrój-Dobosz
Irena
I
Neuromuscular Unit, Institute of Experimental and Clinical Medicine, Polish Academy of Sciences, Warszawa, Poland. neurmyol@cmdik.pan.pl
Hausmanowa-Petrusewicz
Irena
I
D000818:Animals; D016189:Dystrophin; D006801:Humans; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*
D016189:Dystrophin; D052248:Nitric Oxide Synthase Type I