The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy. 2020

Mikhail V Dubinin, and Eugeny Yu Talanov, and Kirill S Tenkov, and Vlada S Starinets, and Natalia V Belosludtseva, and Konstantin N Belosludtsev
Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008931 Mitochondria, Muscle Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available. Sarcosomes,Mitochondrion, Muscle,Muscle Mitochondria,Muscle Mitochondrion,Sarcosome
D011282 Pregnenediones Unsaturated pregnane derivatives containing two keto groups on side chains or ring structures. Diketopregnenes,Dioxopregnenes
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003576 Electron Transport Complex IV A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane. Cytochrome Oxidase,Cytochrome aa3,Cytochrome-c Oxidase,Cytochrome Oxidase Subunit III,Cytochrome a,a3,Cytochrome c Oxidase Subunit VIa,Cytochrome-c Oxidase (Complex IV),Cytochrome-c Oxidase Subunit III,Cytochrome-c Oxidase Subunit IV,Ferrocytochrome c Oxygen Oxidoreductase,Heme aa3 Cytochrome Oxidase,Pre-CTOX p25,Signal Peptide p25-Subunit IV Cytochrome Oxidase,Subunit III, Cytochrome Oxidase,p25 Presequence Peptide-Cytochrome Oxidase,Cytochrome c Oxidase,Cytochrome c Oxidase Subunit III,Cytochrome c Oxidase Subunit IV,Oxidase, Cytochrome,Oxidase, Cytochrome-c,Signal Peptide p25 Subunit IV Cytochrome Oxidase,p25 Presequence Peptide Cytochrome Oxidase
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000081406 Peptidyl-Prolyl Isomerase F A member of the cyclophilins family of isomerases which plays a role in the regulation of the permeability transition pore in mitochondria. The protein has the alias name cyclophilin D which is also the alias name for the related protein Peptidyl-Prolyl Isomerase D. Cyclophilin D, PPIF,Cyclophilin F,Mitochondrial Cyclophilin D,PPIF Cyclophilin,Peptidylprolyl Isomerase F,Cyclophilin D, Mitochondrial,Cyclophilin, PPIF,D, PPIF Cyclophilin,PPIF Cyclophilin D,Peptidyl Prolyl Isomerase F
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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