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Muscular Dystrophy And Exercise-induced Muscle Fatigue Have More In Common Than You Might Think

Date:
March 3, 2009
Source:
Journal of Clinical Investigation
Summary:
Duchenne muscular dystrophy (DMD), which is a severe disorder characterized by rapid progression of muscle weakness that ultimately leads to death, is caused by genetic mutations that result in the absence of the protein dystrophin. Loss of localization of the muscle-related molecule nNOS at the muscle cell membrane (which is known as the sarcolemma) is also observed in DMD and has been linked to muscle damage. What determines the localization of nNOS in muscle cells is not well understood.

Duchenne muscular dystrophy (DMD), which is a severe disorder characterized by rapid progression of muscle weakness that ultimately leads to death, is caused by genetic mutations that result in the absence of the protein dystrophin.

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Loss of localization of the muscle-related molecule nNOS at the muscle cell membrane (which is known as the sarcolemma) is also observed in DMD and has been linked to muscle damage. What determines the localization of nNOS in muscle cells is not well understood.

However, in a new study, Dongsheng Duan and his colleagues, at the University of Missouri, Columbia, have determined that specific regions of dystrophin anchor nNOS to the sarcolemma, providing new avenues of research for the development of DMD therapies.

The research is published Feb. 23, 2009, in the Journal of Clinical Investigation.

In the study, analysis of mutant forms of dystrophin lacking specific regions indicated that regions known as spectrin-like repeats 16 and 17 (R16/17) were necessary for localizing nNOS to the sarcolemma. Further, treatment of a mouse model of DMD with gene therapy to introduce the region R16/17 of dystrophin restored muscle strength and exercise performance. This targeting of nNOS to the sarcolemma enabled nNOS to improve blood flow through the muscles during exercise.

In an accompanying commentary, Ahlke Heydemann and Elizabeth McNally, at the University of Chicago, Chicago, indicate that in addition to providing targets for DMD, these results also "advance our understanding of exercise-induced muscle fatigue and treatment."


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal References:

  1. Lai et al. Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI36612
  2. McNally et al. NO more muscle fatigue. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38618

Cite This Page:

Journal of Clinical Investigation. "Muscular Dystrophy And Exercise-induced Muscle Fatigue Have More In Common Than You Might Think." ScienceDaily. ScienceDaily, 3 March 2009. <www.sciencedaily.com/releases/2009/02/090224004346.htm>.
Journal of Clinical Investigation. (2009, March 3). Muscular Dystrophy And Exercise-induced Muscle Fatigue Have More In Common Than You Might Think. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2009/02/090224004346.htm
Journal of Clinical Investigation. "Muscular Dystrophy And Exercise-induced Muscle Fatigue Have More In Common Than You Might Think." ScienceDaily. www.sciencedaily.com/releases/2009/02/090224004346.htm (accessed November 27, 2014).

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