Mapping and Sequencing of Gangliosides from Anencephaly by Electrospray Ionization High Capacity Ion Trap Mass Spectrometry
Congenital malformation referred to as anencephaly is a neural tube defect that occurs when the cephalic end of the neural tube fails to close, resulting in the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain—the largest part of the brain consisting mainly of the cerebrum, which is responsible for thinking and coordination. Although some individuals with anencephaly may be born with a rudimentary brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. Gangliosides (GGs) are sialylated glycosphingolipids present in the cell plasma membrane, responsible for the modulation of the cell signal transduction events. GGs act as receptors of interferon, epidermal growth factor, nerve growth factor and are differently expressed in various pathological states of central nervous system (CNS) acting as biomarkers of CNS disorders. In this study a native GG mixture extracted and purified from a histopathologically-defined anencephalic fetal brain remnant was analyzed by electrospray ionization high capacity ion trap mass spectrometry. Structural data upon disease-associated species were collected by multiple stage collision-induced dissociation of the molecular ions. As a control a native GG mixture from a normal fetal brain in the same developmental stage was used. Comparative screening and sequencing revealed the differential expression of the GGs in aberrant vs. healthy tissue and provided accurate information upon the structure of several anencephaly-associated species.
KeywordsHPLC Glycerol Hydration Carbohydrate Electrophoresis
Unable to display preview. Download preview PDF.
- 5.S. Liang, M. Wang, R.I. Tapping, V. Stepensky, H.F. Nawar, M. Triantafilou, K. Triantafilou, T.D. Connell, G. Hajishengallis, Ganglioside GD1a is an essential coreceptor for Toll-like receptor 2 signaling in response to the B subunit of type IIb enterotoxin, J. Biol. Chem. 282 (2007) 7532-7542.CrossRefPubMedGoogle Scholar
- 13.Z. Vukeliü, S. Kalanj-Bognar, M. Froesch, L. Bîndila, B. Radiü, M. Allen, J. PeterKataliniü, A.D. Zamfir. Human gliosarcoma-associated ganglioside composition is complex and distinctive as evidenced by high-performance mass spectrometric determination and structural characterization, Glycobiology 17 (2007) 504-515.CrossRefGoogle Scholar
- 14.K.M. Hedberg, R. Mahesparan, T.A. Read, B.B. Tysnes, F. Thorsen, T. Visted, R. Bjerkvig, P. Fredman, The glioma-associated gangliosides 3'-isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains, Neuropathol. Appl. Neurobiol. 27 (2001) 451-464.CrossRefPubMedGoogle Scholar
- 15.A. Markowska-Woyciechowska, A. Bronowicz, M. Ugorski, E. Gamian, P. JabáoĔski, Study on ganglioside composition in brain tumours supra- and infratentorial, Neurol. Neurochir. Pol. 34 (2000) 24-30.Google Scholar
- 22.P.B. O'Connor, B.A. Budnik, V.B. Ivleva, P. Kaur, S.C. Moyer, J.L. Pittman, C.E. Costello, A high pressure matrix-assisted laser desorption ion source for Fourier transform mass spectrometry designed to accommodate large targets with diverse surfaces, J. Am. Soc. Mass Spectrom. 15 (2004) 128-132.CrossRefPubMedGoogle Scholar
- 27.Z. Vukeliü, A.D. Zamfir, L. Bindila, M. Froesch, J. Peter-Kataliniü, S. Usuki, R.K. Yu, Screening and sequencing of complex sialylated and sulfated glycosphingolipid mixtures by negative ion electrospray Fourier transform ion cyclotron resonance mass spectrometry, J. Am. Soc. Mass Spectrom. 16 (2005) 571-580.CrossRefGoogle Scholar
- 29.V.B. Ivleva, Y.N. Elkin, B.A. Budnik, S.C. Moyer, P.B. O'Connor, C.E. Costello, Coupling thin-layer chromatography with vibrational cooling matrix-assisted laser desorption/ionization Fourier transform mass spectrometry for the analysis of ganglioside mixtures, Anal. Chem. 76 (2004) 6484-6491.CrossRefPubMedGoogle Scholar
- 30.K. Dreisewerd, J. Müthing, A. Rohlfing, I. Meisen, Z. Vukeliü, J. Peter-Kataliniü, F. Hillenkamp, S. Berkenkamp, Analysis of gangliosides directly from thin-layer chromatography plates by infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry with a glycerol matrix, Anal. Chem. 77 (2005) 4098-4107.CrossRefPubMedGoogle Scholar
- 42.L. Svennerholm, Ganglioside designation, Adv. Exptl. Med. Biol. 125 (1980) 125-211.Google Scholar
- 43.IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCNB). Eur. J. Biochem. (1998) 257-293Google Scholar