PubMed:22484966
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/22484966","sourcedb":"PubMed","sourceid":"22484966","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/22484966","text":"Abnormal gangliosides are localized in lipid rafts in Sanfilippo (MPS3a) mouse brain.\nAllogenic 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 (G(M3)) 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 \u003e90 % C18:0 fatty acid, suggesting a neuronal origin. Further analysis also revealed a \u003ethreefold increase in the late-endosome marker bis (monoacylglycerol) phosphate (\u003e70 % 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.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_22484966_2_0","span":{"begin":490,"end":500},"obj":"expanded"},{"id":"SS2_22484966_2_0","span":{"begin":502,"end":504},"obj":"abbr"},{"id":"SS1_22484966_5_0","span":{"begin":1339,"end":1359},"obj":"expanded"},{"id":"SS2_22484966_5_0","span":{"begin":1361,"end":1363},"obj":"abbr"}],"relations":[{"id":"AE1_22484966_2_0","pred":"abbreviatedTo","subj":"SS1_22484966_2_0","obj":"SS2_22484966_2_0"},{"id":"AE1_22484966_5_0","pred":"abbreviatedTo","subj":"SS1_22484966_5_0","obj":"SS2_22484966_5_0"}],"attributes":[{"subj":"SS1_22484966_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_22484966_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_22484966_5_0","pred":"source","obj":"Allie"},{"subj":"SS2_22484966_5_0","pred":"source","obj":"Allie"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#93ecb7","default":true}]}]}}