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Sulfatide with short fatty acid dominates in astrocytes and neurons

Artikel i vetenskaplig tidskrift
Författare Giorgis Isaac
Zarah Pernber
Volkmar Gieselmann
Elisabeth Hansson
Jonas Bergquist
Jan-Eric Månsson
Publicerad i FEBS Journal
Volym 273
Nummer/häfte 8
Sidor 1782-1790
ISSN 1742-464X
Publiceringsår 2006
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1782-1790
Språk en
Länkar dx.doi.org/10.1111/j.1742-4658.2006...
Ämnesord a-deficient mice, electrospray-ionization, mass-spectrometry, metachromatic leukodystrophy, primary cultures, rat cerebellum, white-matter, brain, differentiation, sulfoglycolipids, Animals, Astrocytes, metabolism, ultrastructure, Cells, Cultured, Cerebroside-Sulfatase, genetics, physiology, Fatty Acids, Female, Leukodystrophy, Metachromatic, metabolism, pathology, Male, Mice, Inbred C57BL, Knockout, Microscopy, Electron, Transmission, Neurons, ultrastructure, Spectrometry, Mass, Electrospray Ionization, Stearic Acids, chemistry, Sulfoglycosphingolipids, metabolism
Ämneskategorier Cell- och molekylärbiologi, Medicin och Hälsovetenskap

Sammanfattning

Glycosphingolipids are located in cell membranes and the brain is especially enriched. We speculated that the subcellular location of glycosphingolipids depends on their fatty acid chain length because their sugar residues are constant, whereas fatty acid chain length can vary within the same molecule. To test this hypothesis we analysed the glycosphingolipid sulfatide, which is highly abundant in myelin and has mostly long fatty acids. We used a negative ion electrospray tandem mass spectrometry precursor ion scan to analyse the molecular species of sulfatide in cultured astrocytes and a mouse model of the human disease metachromatic leukodystrophy. In these arylsulfatase A (ASA)-deficient mice sulfatide accumulates intracellularly in neurons and astrocytes. Immunocytochemistry was also performed on cultured astrocytes and analysed using confocal laser scanning microscopy. Analyses of the molecular species showed that cultured astrocytes contained sulfatide with a predominance of stearic acid (C18), which was located in large intracellular vesicles throughout the cell body and along the processes. The same was seen in ASA-deficient mice, which accumulated a higher proportion (15 mol% compared with 8 mol% in control mice) of sulfatide with stearic acid. We conclude that the major fatty acid composition of sulfatide differs between white and grey matter, with neurons and astrocytes containing mostly short-chain fatty acids with an emphasis on stearic acid. Based on our results, we speculate that the fatty acid chain length of sulfatide might determine its intracellular (short chain) or extracellular (long chain) location and thereby its functions.

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