Back to Search
Start Over
Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2016 Jul; Vol. 73 (13), pp. 2583-99. Date of Electronic Publication: 2016 Jan 23. - Publication Year :
- 2016
-
Abstract
- Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD. Fast myofibers of mdx mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca(2+) levels, immunoreactivity to phosphorylated p65 (active NF-κB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control mdx muscles. Nonetheless, the hanging test performance of mdx Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice was significantly better than that of control mdx Cx43(fl/fl)Cx45(fl/fl) mice. All three Cxs found in skeletal muscles of mdx mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD.
- Subjects :
- Animals
Cell Death
Connexins metabolism
Dystrophin analysis
Dystrophin metabolism
Female
Humans
Male
Mice, Inbred mdx
Muscle Fibers, Skeletal metabolism
Muscle Fibers, Skeletal pathology
Muscle, Skeletal metabolism
Muscular Dystrophy, Duchenne metabolism
NF-kappa B analysis
NF-kappa B metabolism
Receptors, Purinergic P2X7 analysis
Receptors, Purinergic P2X7 metabolism
Apoptosis
Connexins analysis
Muscle, Skeletal pathology
Muscular Dystrophy, Duchenne pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 73
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 26803842
- Full Text :
- https://doi.org/10.1007/s00018-016-2132-2