Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IkappaBalpha/NF-kappaB survival pathway in skeletal muscle

Détails

ID Serval
serval:BIB_07EF9626C924
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IkappaBalpha/NF-kappaB survival pathway in skeletal muscle
Périodique
Journal of Molecular Medicine
Auteur⸱e⸱s
Baghdiguian  S., Richard  I., Martin  M., Coopman  P., Beckmann  J. S., Mangeat  P., Lefranc  G.
ISSN
0946-2716 (Print)
Statut éditorial
Publié
Date de publication
06/2001
Volume
79
Numéro
5-6
Pages
254-61
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Jun
Résumé
Limb girdle muscular dystrophies (LGMDs) are a group of clinically heterogeneous genetic diseases characterized by progressive weakness and atrophy of scapular and pelvic muscles, with either a dominant or recessive autosomic mode of inheritance. The first symptoms of the disorder appear during the first 20 years of life and progresses gradually, and a walking disability develops 10-20 years later. The gene responsible for LGMD2A has been identified and encodes calpain 3, a protease expressed mainly in skeletal muscle. Apoptotic myonuclei were recently detected in muscular biopsy specimens of LGMD2A patients, and apoptosis was found to be correlated with altered subcellular distribution of inhibitory protein kappaBalpha (IkappaBalpha) and nuclear factor kappaB (NF-kappaB), resulting in sarcoplasmic sequestration of NF-kappaB. Calpain 3 dependent IkappaBalpha degradation was reconstituted in vitro, supporting a possible in vivo sequence of events leading from calpain 3 deficiency to IkappaBkappa accumulation, prevention of nuclear translocation of NF-kappaB, and ultimately apoptosis. Therefore calpain 3, present in healthy muscle as sarcoplasmic and nuclear forms, may control IkappaBalpha turnover and indirectly regulate NF-kappaB dependent expression of survival genes. Recent data reported from a new model of LGMD2A in mice and from other muscular disorders strengthen understanding of the molecular links between calpain 3 and the Ikappaalpha/NF-kappaB pathway. Finally, in light of the lack of apoptosis observed in inflammatory myopathies, a unifying model for the control of cell survival in muscle is proposed and discussed
Mots-clé
Animals Apoptosis Calpain/deficiency/metabolism Cell Survival DNA-Binding Proteins/*metabolism Humans *I-kappa B Proteins *Isoenzymes Models, Biological *Muscle Proteins Muscle, Skeletal/*metabolism/pathology/physiopathology Muscular Dystrophies/enzymology/metabolism/pathology/*physiopathology Myositis/metabolism/pathology NF-kappa B/*metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 16:18
Dernière modification de la notice
20/08/2019 12:30
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