Duchenne muscular dystrophy is associated with the inhibition of calcium uniport in mitochondria and an increased sensitivity of the organelles to the calcium-induced permeability transition

Publication date: Available online 8 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mikhail V. Dubinin, Eugeny Yu. Talanov, Kirill S. Tenkov, Vlada S. Starinets, Irina B. Mikheeva, Mars G. Sharapov, Konstantin N. BelosludtsevAbstractDuchenne muscular dystrophy (DMD) is characterized by a pronounced and progressive degradation of the structure of skeletal muscles, which decreases their strength and lowers endurance of the organism. At muscular dystrophy, mitochondria are known to undergo significant functional changes, which is manifested in a decreased efficiency of oxidative phosphorylation and impaired energy metabolism of the cell. It is believed that the DMD-induced functional changes of mitochondria are mainly associated with the dysregulation of Ca2+ homeostasis. This work examines the kinetic parameters of Ca2+ transport and the opening of the Ca2+-dependent MPT pore in the skeletal-muscle mitochondria of the dystrophin-deficient C57BL/10ScSn-mdx mice. As compared to the organelles of wild-type animals, skeletal-muscle mitochondria of mdx mice have been found to be much less efficient in respect to Ca2+ uniport, with the kinetics of Na+-dependent Ca2+ efflux not changing. The data obtained indicate that the decreased rate of Ca2+ uniport in the mitochondria of mdx mice may be associated with the increased level of the dominant negative subunit of Ca2+ uniporter (MCUb). The experiments have also shown that in mdx mice, ske...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Aktan G Abstract Dropped head syndrome can be seen in many neuromuscular diseases. However, there are very few diseases in which neck extensors are weak among neuromuscular diseases. A 7 years old boy who had weakness of the neck extensor muscles, creatinine kinase elevation and dystrophy findings in biopsy followed up with the preliminary diagnosis of muscular dystrophy is presented. We detected p.N456K (c.1368C> A) heterozygote mutation by the gene sequencing in the Lamin A/C assocıated (LMNA) gene. This mutation was previously reported as Emery-Dreifuss muscular dystrophy. PMID: 32253878 [PubMed - in process]
Source: The Turkish Journal of Pediatrics - Category: Pediatrics Authors: Tags: Turk J Pediatr Source Type: research
This article reviews the diagnosis and treatment of heart disease in Duchenne muscular dystrophy as well as emerging therapies.
Source: Current Heart Failure Reports - Category: Cardiology Source Type: research
Conditions:   Muscular Dystrophy, Duchenne;   DMD Intervention:   Drug: viltolarsen Sponsor:   NS Pharma, Inc. Available
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Duchenne Muscular Dystrophy Intervention:   Drug: Ataluren Sponsor:   PTC Therapeutics Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Muscular Dystrophy, Duchenne;   DMD Intervention:   Drug: viltolarsen Sponsor:   NS Pharma, Inc. Available
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Duchenne Muscular Dystrophy Intervention:   Drug: Ataluren Sponsor:   PTC Therapeutics Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Muscular Dystrophy, Duchenne;   DMD Intervention:   Drug: viltolarsen Sponsor:   NS Pharma, Inc. Available
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Duchenne Muscular Dystrophy Intervention:   Drug: Ataluren Sponsor:   PTC Therapeutics Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular d...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atroph...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
More News: Calcium | Mitochondria | Molecular Biology | Muscular Dystrophy | Reflex Sympathetic Dystrophy