Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro
- Brogden, Graham Fish Disease Research Unit, University of Veterinary Medicine Hannover, Buenteweg 17, D-30559 Hannover, Germany
- Shammas, Hadeel Department of Paediatrics, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
- Maalouf, Katia Department of Paediatrics, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
- Naim, Samara L. Faculty of Science, University of Fribourg, Switzerland
- Wetzel, Gabi Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany
- Amiri, Mahdi Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany
- von Köckritz-Blickwede, Maren Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany
- Das, Anibh M. Department of Paediatrics, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany
- Naim, Hassan Y. Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany
- 2017-4-28
Published in:
- Bioscience Reports. - Portland Press Ltd.. - 2017, vol. 37, no. 2
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1042/bsr20160402
- ISSN 0144-8463
- Persistent URL
- https://sonar.ch/global/documents/159377
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