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|Title:||Effect of lysosomal storage on bis(monoacylglycero)phosphate|
|Citation:||Biochemical Journal, 2008; 411(Part 1):71-78|
|Peter J. Meikle, Stephen Duplock, David Blacklock, Phillip D. Whitfield, Gemma MacIntosh, John J. Hopwood and Maria Fuller|
|Abstract:||BMP [bis(monoacylglycero)phosphate] is an acidic phospholipid and a structural isomer of PG (phosphatidylglycerol), consisting of lysophosphatidylglycerol with an additional fatty acid esterified to the glycerol head group. It is thought to be synthesized from PG in the endosomal/lysosomal compartment and is found primarily in multivesicular bodies within the same compartment. In the present study, we investigated the effect of lysosomal storage on BMP in cultured fibroblasts from patients with eight different LSDs (lysosomal storage disorders) and plasma samples from patients with one of 20 LSDs. Using ESI-MS/MS (electrospray ionization tandem MS), we were able to demonstrate either elevations or alterations in the individual species of BMP, but not of PG, in cultured fibroblasts. All affected cell lines, with the exception of Fabry disease, showed a loss of polyunsaturated BMP species relative to mono-unsaturated species, and this correlated with the literature reports of lysosomal dysfunction leading to elevations of glycosphingolipids and cholesterol in affected cells, processes thought to be critical to the pathogenesis of LSDs. Plasma samples from patients with LSDs involving storage in macrophages and/or with hepatomegaly showed an elevation in the plasma concentration of the C(18:1)/C(18:1) species of BMP when compared with control plasmas, whereas disorders involving primarily the central nervous system pathology did not. These results suggest that the release of BMP is cell/tissue-specific and that it may be useful as a biomarker for a subset of LSDs.|
|Keywords:||Cells, Cultured; Lysosomes; Fibroblasts; Macrophages; Humans; Lysosomal Storage Diseases; Glycerophosphates; Lysophospholipids; Spectrometry, Mass, Electrospray Ionization|
|Description:||Copyright © The Authors|
|Appears in Collections:||Paediatrics publications|
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