title: Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis.
abstract: Gangliosides are sialylated membrane glycosphingolipids especially abundant in mammalian brain tissue. Sialic acid O-acetylation is one of the most common structural modifications of gangliosides which considerably influences their chemical properties. In this study, gangliosides extracted from brain tissue of mice with altered ganglioside biosynthesis (St8sia1 null and B4galnt1 null mice) were structurally characterized and their acetylation pattern was analyzed. Extracted native and alkali-treated gangliosides were resolved by high performance thin layer chromatography. Ganglioside mixtures as well as separated individual ganglioside fractions were further analyzed by tandem mass spectrometry. Several O-acetylated brain ganglioside species were found in knockout mice, not present in the wild-type mice. To the best of our knowledge this is the first report on the presence of O-acetylated GD1a in St8sia1 null mice and O-acetylated GM3 species in B4galnt1 null mice. In addition, much higher diversity of abnormally accumulated brain ganglioside species regarding the structure of ceramide portion was observed in knockout versus wild-type mice. Obtained findings indicate that the diversity of brain ganglioside structures as well as acetylation patterns in mice with altered ganglioside biosynthesis, is even higher than previously reported. Further investigation is needed in order to explore the effects of acetylation on ganglioside interactions with other molecules and consequently the physiological role of acetylated ganglioside species.
authors.affiliation: Department for Chemistry and Biochemistry, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, 10000 Zagreb, Croatia. Electronic address: kristina.mlinac@mef.hr.
authors.forename: Kristina
authors.initials: K
authors.lastname: Mlinac
authors.forename: Dragana
authors.initials: D
authors.lastname: Fabris
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Vukelić
authors.forename: Marko
authors.initials: M
authors.lastname: Rožman
authors.forename: Marija
authors.initials: M
authors.lastname: Heffer
authors.forename: Svjetlana Kalanj
authors.initials: SK
authors.lastname: Bognar
mesh_terms: D000107:Acetylation; D000818:Animals; D001923:Brain Chemistry; D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D005732:Gangliosides; D017350:N-Acetylgalactosaminyltransferases; C000590840:beta-1,4-N-acetyl-galactosaminyl transferase 1, mouse; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
keywords: Brain gangliosides; Mass spectrometric characterization; O-acetylated ganglioside species; O-acetylation patterns; St8sia1 null and B4galnt1 null mice