Abstract
Duchenne muscular dystrophy (DMD) is a severe hereditary disease caused by a lack of dystrophin, a protein essential for myocyte integrity. Mitochondrial dysfunction is reportedly responsible for DMD. This study examines the effect of glucocorticoid deflazacort on the functioning of the skeletal-muscle mitochondria of dystrophin-deficient mdx mice and WT animals. Deflazacort administration was found to improve mitochondrial respiration of mdx mice due to an increase in the level of ETC complexes (complexes III and IV and ATP synthase), which may contribute to the normalization of ATP levels in the skeletal muscle of mdx animals. Deflazacort treatment improved the rate of Ca2+ uniport in the skeletal muscle mitochondria of mdx mice, presumably by affecting the subunit composition of the calcium uniporter of organelles. At the same time, deflazacort was found to reduce the resistance of skeletal mitochondria to MPT pore opening, which may be associated with a change in the level of ANT2 and CypD. In this case, deflazacort also affected the mitochondria of WT mice. The paper discusses the mechanisms underlying the effect of deflazacort on the functioning of mitochondria and contributing to the improvement of the muscular function of mdx mice.
Highlights
Duchenne muscular dystrophy (DMD) is the most prevalent muscular dystrophy afflicting ~1 in3500–5000 live born males [1,2]
We examined the effect of deflazacort administration on the level of proteins that form the complexes of the respiratory chain of mitochondria in the skeletal muscle of the studied animal
We found a similar pattern in the case of found that skeletal muscle mitochondria of dystrophin-deficient mice show an increase in We the have level found that(inactive skeletal muscle of Ca dystrophin-deficient mice show an increase the level of MCUb channelmitochondria subunit of the uniporter), which is accompanied by a in significant
Summary
Duchenne muscular dystrophy (DMD) is the most prevalent muscular dystrophy afflicting ~1 in3500–5000 live born males [1,2]. Duchenne muscular dystrophy (DMD) is the most prevalent muscular dystrophy afflicting ~1 in. Regarded as a debilitating and fatal skeletal muscle disease, DMD is characterised by muscular weakness, exercise intolerance, and progressive deterioration of skeletal muscle. DMD is caused by large deletions and small forms of other mutations (deletions, duplications, insertions, and substitutions) in the dystrophin gene located on the short arm of the X-chromosome. The protein encoded by this gene is involved in the formation of a complex functional network (the so-called dystrophin-associated protein complex) which ensures the integrity and rigidity of muscle fibers. Dystrophin deficiency and secondary reduction of these glycoproteins [3]. Render the myoctes and their fibers more susceptible to damage as they become structurally unstable and exceedingly porous to the extracellular environment.
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