Alisporivir Improves Mitochondrial Function in Skeletal Muscle of mdx Mice but Suppresses Mitochondrial Dynamics and Biogenesis.
Mikhail V. Dubinin,Vlada S. Starinets,Eugeny Yu. Talanov,I. B. Mikheeva,Natalia V. Belosludtseva,Konstantin N. Belosludtsev +5 more
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TLDR
In this article, the effect of intraperitoneal administration of a non-immunosuppressive inhibitor of calcium-dependent mitochondrial permeability transition (MPT) pore alisporivir on the state of skeletal muscles and the functioning of mitochondria in dystrophin-deficient mdx mice was studied.Abstract:
Mitigation of calcium-dependent destruction of skeletal muscle mitochondria is considered as a promising adjunctive therapy in Duchenne muscular dystrophy (DMD). In this work, we study the effect of intraperitoneal administration of a non-immunosuppressive inhibitor of calcium-dependent mitochondrial permeability transition (MPT) pore alisporivir on the state of skeletal muscles and the functioning of mitochondria in dystrophin-deficient mdx mice. We show that treatment with alisporivir reduces inflammation and improves muscle function in mdx mice. These effects of alisporivir were associated with an improvement in the ultrastructure of mitochondria, normalization of respiration and oxidative phosphorylation, and a decrease in lipid peroxidation, due to suppression of MPT pore opening and an improvement in calcium homeostasis. The action of alisporivir was associated with suppression of the activity of cyclophilin D and a decrease in its expression in skeletal muscles. This was observed in both mdx mice and wild-type animals. At the same time, alisporivir suppressed mitochondrial biogenesis, assessed by the expression of Ppargc1a, and altered the dynamics of organelles, inhibiting both DRP1-mediated fission and MFN2-associated fusion of mitochondria. The article discusses the effects of alisporivir administration and cyclophilin D inhibition on mitochondrial reprogramming and networking in DMD and the consequences of this therapy on skeletal muscle health.read more
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Bioactive Peptides: Synthesis, Sources, Applications, and Proposed Mechanisms of Action
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BKCa Activator NS1619 Improves the Structure and Function of Skeletal Muscle Mitochondria in Duchenne Dystrophy
Mikhail V. Dubinin,Vlada S. Starinets,Natalia V. Belosludtseva,I. B. Mikheeva,Yuliya A Chelyadnikova,Anastasia D Igoshkina,Aliya B. Vafina,A. A. Vedernikov,Konstantin N. Belosludtsev +8 more
TL;DR: In this paper , the role of the BKCa activator NS1619 in the development of Duchenne muscular dystrophy (DMD) was examined in dystrophin-deficient mdx mice.
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The Effect of Uridine on the State of Skeletal Muscles and the Functioning of Mitochondria in Duchenne Dystrophy
Mikhail V. Dubinin,Vlada S. Starinets,Natalia V. Belosludtseva,I. B. Mikheeva,Yuliya A Chelyadnikova,Daria K. Penkina,A. A. Vedernikov,Konstantin N. Belosludtsev +7 more
TL;DR: It is found that chronic uridine administration reduced fibrosis in the skeletal muscles of mdx mice, but it had no effect on the intensity of degeneration/regeneration cycles and inflammation, pseudohypetrophy, and muscle strength of the animals.
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Comparison of structural properties of cyclosporin A and its analogue alisporivir and their effects on mitochondrial bioenergetics and membrane behavior.
Mikhail V. Dubinin,Vyacheslav A. Sharapov,Anna I. Ilzorkina,S.V. Efimov,Vladimir V. Klochkov,Sergey V. Gudkov,Konstantin N. Belosludtsev +6 more
TL;DR: In this paper , the effect of cyclosporin A (CsA) and its non-immunosuppressive analogue alisporivir (Ali) on the functioning of rat skeletal muscle mitochondria was investigated.
Journal ArticleDOI
Analysis of Mitochondrial Function, Structure, and Intracellular Organization In Situ in Cardiomyocytes and Skeletal Muscles
Andrey V. Kuznetsov,Sabzali Javadov,Raimund Margreiter,Judith Hagenbuchner,Michael J. Ausserlechner +4 more
TL;DR: This review summarizes previous studies and discusses existing approaches and methods for the analysis of mitochondrial function, structure, and intracellular organization in situ.
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