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MKT-077 normalizes mitochondrial function and mitigates cardiac pathology in mdx mice

BIOCELL 2024年第12期48卷 1815-1825页

作者： MIKHAIL V.DUBININ IRINA B.MIKHEEVA ANASTASIA E.STEPANOVA NATALIA V.MIKINA DANIIL V.SUSHENTSOV VYACHESLAV A.SHARAPOV ALENA A.CHEREPANOVA VALENTIN V.LOSKUTOV KONSTANTIN N.BELOSLUDTSEV Department of Biochemistry Cell Biologyand MicrobiologyMari State UniversityYoshkar-Ola424001Russia Laboratory of Mitochondrial Transport Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino142290Russia

Objectives:Duchenne muscular dystrophy(DMD)is characterized by the development of cardiac pathology secondarily expressed in mitochondrial *** treatment includes support for mitochondrial *** purpose of this work was to evaluate the effects of the lipophilic cation MKT-077,capable of modulating mitochondrial activity,on the structure and function of cardiac mitochondria in mdx and wild-type mice,as well as the state of this ***:Animals were divided into 4 groups:wild type(WT),WT+5 mg/kg MKT-077,mdx,mdx+5 mg/kg ***-077 was administered intraperitoneally daily for 28 ***,we assessed the parameters of the functioning of the cardiac mitochondria of mice,the expression of genes encoding proteins involved in mitochondrial communication,as well as the histology and ultrastructure of the myocardium and heart ***:MKT-077 was shown to reverse mitochondrial hyperfunctionalization in mdx mice,reducing respiratory parameters to WT ***-077 also inhibited mitochondrial respiration in the hearts of WT ***-077 administration was accompanied by a tendency to normalize calcium retention capacity in the cardiac mitochondria of mdx *** ultrastructure and gene signature of mdx+MKT077 animals demonstrated increased *** noted changes in the sarcoplasmic reticulum(SR)/mitochondria contacts,accompanied by differential changes in the level of genes encoding proteins involved in the communication of these *** effect of MKT-077 was accompanied by normalization of the relative heart weight of mdx mice,a decrease in the level of fibrosis,and a tendency toward normalization of heart ***:MKT-077-induced reversal of cardiac mitochondrial hyperfunctionalization in mdx mice may promote a healthy-like state of the myocardium in these animals.

关键词： Duchenne muscular dystrophy mdx mice Cardiac mitochondria MKT-077

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