Glucocorticoid treatment induces expression of small heat shock proteins in human satellite cell populations: consequences for a desmin-related myopathy involving the R120G alpha B-crystallin mutation.
A missense mutation (R120G) of the molecular chaperone alpha B-crystallin has recently been linked to a familial form of desmin-related myopathy characterized by intrasarcoplasmic aggregates of desmin. It was previously demonstrated that the mutant R120G had a defective chaperone-like function. However, the cellular and physiopathological consequences of R120G mutant expression in human muscle cells are as yet unclear. Thus, we developed a cellular model for the study of this R120G alpha B-crystallin-related desmin-related myopathy. We demonstrate that dexamethasone enhances alpha B-crystallin and HSP27 expression in normal and desmin-related myopathy-derived muscle cells. In the undifferentiated desmin-related myopathy satellite cell population no intracytoplasmic aggregates were observed. However, in differentiated satellite cells derived from a related myopathy patient, we observed an enhanced plasma membrane localization of alpha B-crystallin following glucocorticoid. We also observed that the protective effect against stress of alpha B-crystallin is altered upon glucocorticoid-induced small heat shock protein expression for the desmin-related myopathy-derived cells.
Nédellec
Patrick
P
Laboratoire Cytosquelette et Développement, Université Paris VI, CNRS UMR 7000, Faculté de Médecine Pitié-Salpêtrière, 105 Boulevard De l'Hôpital, 75634 Cedex 13, Paris, France.
Edling
Ylva
Y
Perret
Emmanuelle
E
Fardeau
Michel
M
Vicart
Patrick
P
D000328:Adult; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D003459:Crystallins / Q000235:genetics* / Q000378:metabolism; D003893:Desmin / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000378:metabolism; D012016:Reference Values; D027161:Satellite Cells, Perineuronal / Q000378:metabolism* / Q000502:physiology
D003459:Crystallins; D003893:Desmin; D005938:Glucocorticoids; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D003907:Dexamethasone