Autophagosome maturation is impaired in Fabry disease.

Détails

ID Serval
serval:BIB_D1494606A253
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Autophagosome maturation is impaired in Fabry disease.
Périodique
Autophagy
Auteur(s)
Chevrier Marc, Brakch Noureddine, Lesueur Celine, Genty Damien, Ramdani Yasmina, Moll Solange, Djavaheri-Mergny Mojgan, Brasse-Lagnel Carole, Laquerriere Annie, Barbey Frederic, Bekri Soumeya
ISSN
1554-8635[electronic], 1554-8627[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
6
Numéro
5
Pages
589-599
Langue
anglais
Résumé
Fabry disease is a lysosomal storage disorder (LSD) caused by a deficiency in alpha-galactosidase A. The disease is characterized by severe major organ involvement, but the pathologic mechanisms responsible have not been elucidated. Disruptions of autophagic processes have been reported for other LSDs, but have not yet been investigated in Fabry disease. Renal biopsies were obtained from five adult male Fabry disease patients before and after three years of enzyme replacement therapy (ERT) with agalsidase alfa. Vacuole accumulation was seen in renal biopsies from all patients compared with control biopsies. Decreases in the number of vacuoles were seen after three years of ERT primarily in renal endothelial cells and mesangial cells. Measurement of the levels of LC3, a specific autophagy marker, in cultured cells from Fabry patients revealed increased basal levels compared to cells from non-Fabry subjects and a larger increase in response to starvation than seen in non-Fabry cells. Starvation in the presence of protease inhibitors did not result in a significant increase in LC3 in Fabry cells, whereas a further increase in LC3 was observed in non-Fabry cells, an observation that is consistent with impaired autophagic flux in Fabry disease. Overexpression of LC3 mRNA in Fabry fibroblasts compared to control cells is consistent with an upregulation of autophagy. Furthermore, LC3 and p62/SQSTM1 (that binds to LC3) staining in renal tissues and in cultured fibroblasts from Fabry patients supports impairment of autophagic flux. These findings suggest that Fabry disease is linked to a deregulation of autophagy.
Mots-clé
Fabry Disease, Enzyme Replacement Therapy, Autophagy, Ubiquitin Pathway, Gb3, Enzyme Replacement Therapy, Agalsidase-Alpha, Cell-Death, Kidney, Marker, Globotriaosylceramide, Accumulation, Dysfunction, Mice, LC3
Pubmed
Web of science
Création de la notice
19/07/2010 15:04
Dernière modification de la notice
20/08/2019 15:51
Données d'usage