Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid
Podbielska, Maria Dasgupta, Somsankar Levery, Steven B. Tourtellotte, Wallace W. Annuk, Heidi Moran, Anthony P. Hogan, Edward L.
Podbielska, Maria
Dasgupta, Somsankar
Levery, Steven B.
Tourtellotte, Wallace W.
Annuk, Heidi
Moran, Anthony P.
Hogan, Edward L.
Publication Date
2010-02-12
Keywords
acetyl-cerebroside, cross-reactivity, electrospray ionization, escherichia coli, fast migrating cerebrosides, glycosphingolipids, inflammation, lipopolysaccharide, multiple sclerosis, multistage mass spectrometry, mycoplasma fermentans, neurological disease, o-antigenic polysaccharide, multiple-sclerosis, molecular mimicry, neutral glycosphingolipids, rat-brain, spectroscopy, expression, lipopolysaccharides, glycolipids, antibodies
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Article
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Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B. Tourtellotte, Wallace W.; Annuk, Heidi; Moran, Anthony P.; Hogan, Edward L. (2010). Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid. Journal of Lipid Research 51 (6), 1394-1406
Abstract
Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked.-Podbielska, M., S. Dasgupta, S. B. Levery, W. W. Tourtellotte, H. Annuk, A. P. Moran, and E. L. Hogan. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid. J. Lipid Res. 2010. 51: 1394-1406.
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Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
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Attribution-NonCommercial-NoDerivs 3.0 Ireland