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.

摘要

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.