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Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro .
- Source :
-
Bioscience reports [Biosci Rep] 2017 Apr 28; Vol. 37 (2). Date of Electronic Publication: 2017 Apr 28 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- It is still not entirely clear how α-galactosidase A (GAA) deficiency translates into clinical symptoms of Fabry disease (FD). The present communication investigates the effects of the mutation N215S in FD on the trafficking and processing of lysosomal GAA and their potential association with alterations in the membrane lipid composition. Abnormalities in lipid rafts (LRs) were observed in fibroblasts isolated from a male patient with FD bearing the mutation N215S. Interestingly, LR analysis revealed that the distribution of cholesterol and flotillin-2 are distinctly altered in the Fabry fibroblasts when compared with that of the wild-type cells. Furthermore, increased levels of glycolipid globotriaosylceramide 3 (Gb3) and sphingomyelin (SM) were observed in non-raft membrane fractions of Fabry cells. Substrate reduction with N -butyldeoxynojirimycin (NB-DNJ) in vitro was capable of reversing these abnormalities in this patient. These data led to the hypothesis that alterations of LRs may contribute to the pathophysiology of Morbus Fabry. Furthermore, it may be suggested that substrate reduction therapy with NB-DNJ might be a promising approach for the treatment of GAA deficiency at least for the selected patients.<br /> (© 2017 The Author(s).)
- Subjects :
- Adult
Cell Membrane metabolism
Cells, Cultured
Fabry Disease metabolism
Fabry Disease physiopathology
Fibroblasts metabolism
Fibroblasts pathology
Glycolipids metabolism
Humans
Male
Oxidation-Reduction
Protein Transport
Sphingomyelins metabolism
Trihexosylceramides metabolism
alpha-Galactosidase metabolism
Cell Membrane pathology
Fabry Disease genetics
Membrane Lipids metabolism
Point Mutation
alpha-Galactosidase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4935
- Volume :
- 37
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioscience reports
- Publication Type :
- Academic Journal
- Accession number :
- 28351893
- Full Text :
- https://doi.org/10.1042/BSR20160402