Article: Plasma protein N-glycan profiles are associated with calendar age, familial longevity and health.L Renee Ruhaak, Hae-Won Uh, Marian Beekman, Cornelis H Hokke, Rudi G J Westendorp, Jeanine Houwing-Duistermaat, Manfred Wuhrer, André M Deelder, P Eline Slagboom[show abstract] [hide abstract]
ABSTRACT: The development of medical interventions for the preservation of disease-free longevity would be facilitated by markers that predict healthy aging. Altered protein N-glycosylation patterns have been found with increasing age and several disease states. Here we investigate whether glycans derived from the total glycoprotein pool in plasma mark familial longevity and distinguish healthy from unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants in the Leiden Longevity Study (LLS) were obtained by glycan release, labeling, and subsequent HPLC analysis with fluorescence detection. After normalization and batch correction, several regression strategies were applied to evaluate associations between glycan patterns, familial longevity, and healthy aging. Two N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma of the offspring of long-lived individuals as compared to controls. These results were not confounded by the altered lipid status or glucose homeostasis of the offspring. Furthermore, a decrease in levels of LC-8 was associated with the occurrence of myocardial infarction (p = 0.049, coefficient = -0.065), indicating that plasma glycosylation patterns do not only mark familial longevity but may also reflect healthy aging. In conclusion, we describe two glycan features, of which increased levels mark familial longevity and decreased levels of one of these features mark the presence of cardiovascular disease.Journal of Proteome Research 12/2010; 10(4):1667-74. · 5.11 Impact Factor
Article: Structural characterization of glycans on omega-1, a major Schistosoma mansoni egg glycoprotein that drives Th2 responses.Moniek H J Meevissen, Manfred Wuhrer, Michael J Doenhoff, Gabriele Schramm, Helmut Haas, André M Deelder, Cornelis H Hokke[show abstract] [hide abstract]
ABSTRACT: Soluble egg antigens (SEA) of the human parasite Schistosoma mansoni are among the strongest natural stimuli of Th2 responses. Omega-1, a major glycoprotein in SEA, initiates these characteristic Th2 responses through conditioning of dendritic cells (DCs). In view of the reported immunomodulatory potential of SEA glycans, we have investigated omega-1 glycosylation, using an approach combining mass spectrometric techniques and enzyme treatments at the glycopeptide level. We demonstrate that omega-1 has two fully occupied N-glycosylation sites, each mainly carrying core-difucosylated diantennary glycans with one or more Lewis X motifs in the antennae. Using a specific approach of nanoscale LC-MS(/MS) and MALDI-TOF(/TOF) MS in combination with exoglycosidase treatments of tryptic glycopeptides, we were able to provide a detailed, site-specific glycosylation analysis of a single, native S. mansoni glycoprotein. The obtained knowledge of the glycans present on omega-1 contributes to a full understanding of the mode of action of this immunomodulatory glycoprotein.Journal of Proteome Research 02/2010; 9(5):2630-42. · 5.11 Impact Factor
Article: Molecular characterisation of kappa-5, a major antigenic glycoprotein from Schistosoma mansoni eggs.G Schramm, J V Hamilton, C I A Balog, M Wuhrer, A Gronow, S Beckmann, V Wippersteg, C G Grevelding, T Goldmann, E Weber, N W Brattig, A M Deelder, D W Dunne, C H Hokke, H Haas, M J Doenhoff[show abstract] [hide abstract]
ABSTRACT: The major immunopathological consequences of infection with Schistosoma mansoni, a T helper type 2 response and granuloma formation leading to fibrotic tissue damage, are caused by the egg stage of the parasite. Three antigens of S. mansoni eggs, termed IPSE/alpha-1, omega-1 and kappa-5, have been found to be the primary targets of the egg-directed antibody response of the host. Here, we report on the isolation, cloning and characterisation of kappa-5. Apart from an uncharacterised mRNA sequence in S. japonicum, no significant similarities of kappa-5 to known sequences from other species were found. In contrast to IPSE/alpha-1 and omega-1, which have been found only in eggs, kappa-5 was present in miracidia as well as in eggs at the mRNA and protein levels. In eggs, isoforms of kappa-5 were observed with both three and four fully occupied N-glycosylation sites, while in miracidia only one isoform with four N-glycans could be detected. Interestingly, in Western blots sera from S. mansoni-infected Africans were reactive against kappa-5 with IgE and IgG isotype antibodies, but against IPSE/alpha-1 and omega-1 only with IgG antibodies. The further characterisation of kappa-5 as one of the three major egg antigens should help to better understand the immunology and immunopathology of schistosomiasis.Molecular and Biochemical Parasitology 08/2009; 166(1):4-14. · 2.55 Impact Factor
Article: Golgi targeting of Drosophila melanogaster β4GalNAcTB requires a DHHC protein family - related protein as a pilot[show abstract] [hide abstract]
ABSTRACT: Cited By (since 1996): 2, Export Date: 15 November 2011, Source: ScopusJournal of Cell Biology. 01/2009; 184:173-183.
Article: Distinct contributions of β4GalNAcTA and β4GalNAcTB to Drosophila glycosphingolipid biosynthesisA. Stolz, N. Haines, A. Pich, K.D. Irvine, C.H. Hokke, A.M. Deelder, R. Gerardy-Schahn, M. Wuhrer, H. Bakker[show abstract] [hide abstract]
ABSTRACT: Cited By (since 1996): 8, Export Date: 15 November 2011, Source: ScopusGlycoconjugate Journal. 01/2008; 25:167-175.