The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy.

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.

• Authors: Mikhail V Dubinin, Eugeny Yu Talanov, Kirill S Tenkov, Vlada S Starinets, Natalia V Belosludtseva, Konstantin N Belosludtsev
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 22 (Nov 19 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33228255 (Publication Type: Journal Article)

Chemical References

• Adenine Nucleotide Translocator 2
• Calcium Channels
• Cyclophilin D
• Pregnenediones
• mitochondrial calcium uniporter
• Adenosine Triphosphate
• Electron Transport Complex IV
• Mitochondrial Proton-Translocating ATPases
• Electron Transport Complex III
• deflazacort
• Calcium

Topics

• Adenine Nucleotide Translocator 2 (genetics, metabolism)
• Adenosine Triphosphate (biosynthesis)
• Animals
• Calcium (metabolism)
• Calcium Channels (genetics, metabolism)
• Cyclophilin D (genetics, metabolism)
• Electron Transport Complex III (genetics, metabolism)
• Electron Transport Complex IV (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Mitochondria, Muscle (drug effects, genetics, metabolism)
• Mitochondrial Proton-Translocating ATPases (genetics, metabolism)
• Muscle, Skeletal (drug effects, metabolism, pathology)
• Muscular Dystrophy, Duchenne (drug therapy, genetics, metabolism, pathology)
• Pregnenediones (pharmacology)