Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/61997

TitleReduced glucosylceramide in the mouse model of Fabry disease: correction by successful enzyme replacement therapy
Author(s)Quinta, Rui
Rodrigues, Daniel
Assunção, Marisa
Macedo, Maria Fatima
Azevedo, Olga
Cunha, Damião
Oliveira, Pedro
Sá Miranda, Maria Clara
KeywordsAdolescent
Adult
Animals
Case-Control Studies
Disease Models, Animal
Fabry Disease
Female
Glucosylceramides
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Treatment Outcome
Young Adult
alpha-Galactosidase
Enzyme Replacement Therapy
Ceramide
Glucosylceramide
Fabry mice
Issue date15-Feb-2014
PublisherElsevier
JournalGene
CitationQuinta, R., Rodrigues, D., Assunção, M., Macedo, M. F., Azevedo, O., Cunha, D., ... & Miranda, M. C. S. (2014). Reduced glucosylceramide in the mouse model of Fabry disease: correction by successful enzyme replacement therapy. Gene, 536(1), 97-104.
Abstract(s)Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of α-Galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if α-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the liver's GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by α-Gal A deficiency.
TypeArticle
URIhttp://hdl.handle.net/1822/61997
DOI10.1016/j.gene.2013.11.073
ISSN0378-1119
e-ISSN1879-0038
Publisher versionhttps://www.sciencedirect.com/science/article/pii/S0378111913015990
Peer-Reviewedyes
AccessRestricted access (Author)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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