Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/76448
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Abnormal gangliosides are localized in lipid rafts in Sanfilippo (MPS3a) mouse brain |
Author: | Dawson, G. Fuller, M. Hemsley, K. Hopwood, J. |
Citation: | Neurochemical Research, 2012; 37(6):1372-1380 |
Publisher: | Kluwer Academic/Plenum Publ |
Issue Date: | 2012 |
ISSN: | 0364-3190 1573-6903 |
Statement of Responsibility: | G. Dawson, M. Fuller, K. M. Helmsley, J. J. Hopwood |
Abstract: | Allogenic stem cell transplantation can reduce lysosomal storage of heparan sulfate-derived oligosaccharides by up to 27 % in Sanfilippo MPS3a brain, but does not reduce the abnormal storage of sialolactosylceramide (GM3) or improve neurological symptoms, suggesting that ganglioside storage is in a non-lysosomal compartment. To investigate this further we isolated the Triton X100-insoluble at 4 °C, lipid raft (LR) fraction from a sucrose-density gradient from cerebral hemispheres of a 7 month old mouse model of Sanfilippo MPS3a and age-matched control mouse brain. HPLC/MS/MS analysis revealed the expected enrichment of normal complex gangliosides, ceramides, galatosylceramides and sphingomyelin enrichment in this LR fraction. The abnormal HS-derived oligosaccharide storage material was in the Triton X100-soluble at 4 °C fractions (8–12),whereas both GM3 and sialo[GalNAc]lactosylceramide (GM2) were found exclusively in the LR fraction (fractions 3 and 4) and were >90 % C18:0 fatty acid, suggesting a neuronal origin. Further analysis also revealed a >threefold increase in the late-endosome marker bis (monoacylglycerol) phosphate (>70 % as C22:6/22:6-BMP) in non-LR fractions 8–12 whereas different forms of the proposed BMP precursor, phosphatidylglycerol (PG) were in both LR and non-LR fractions and were less elevated in MPS3a brain. Thus heparan sulfate-derived oligosaccharide storage is associated with abnormal lipid accumulation in both lysosomal (BMP) and non-lysosomal (GM3 and GM2) compartments. |
Keywords: | Gangliosides Mass-spectrometry Sanfilippo Mouse brain Bis(monoacylglycerol) phosphate Lipid rafts |
Rights: | © Springer Science+Business Media, LLC 2012 |
DOI: | 10.1007/s11064-012-0761-x |
Published version: | http://dx.doi.org/10.1007/s11064-012-0761-x |
Appears in Collections: | Aurora harvest Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.