Glycobiology Advance Access published online on July 21, 2004
Glycobiology, doi:10.1093/glycob/cwh131
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1 Rational Drug Design Program, Department of Bacteriology and Immunology, Haartman Institute and Biomedicum, P.O. Box 63, FIN-00014, University of Helsinki, Finland
* To whom correspondence should be addressed. E-mail: Risto.Renkonen{at}Helsinki.Fi.
The de novo synthesis and expression of sulfo sLex glycan on vascular endothelial glycoproteins has a central role in the initiation of inflammatory reactions, serving as a putative zip code for organ-specific trafficking of leukocytes into sites of inflammation. The synthesis of sulfo sLex requires energy carrying donors, CMP-sialic acid (CMP-SA), GDP-fucose (GDP-Fuc), and adenosine 3'-phosphate 5'-phosphosulphate (PAPS), for donation of sialic acid, fucose and sulfate, respectively. These donors are synthesized in the nucleus or cytosol, and translocated into Golgi by specific transporters where corresponding transferase and proteins as well as enzymatic activities increase upon inflammatory stimuli. Here we analyze the transcriptional co-regulation of CMP-SA, GDP-Fuc, and PAPS transporters with in situ hybridization and real-time PCR in acute inflammation using kidney and heart allografts as model systems. Our results indicate that these three transporters display coordinated transcriptional regulation during the induction of the sulfo sLex glycan biosynthesis. In in silico analysis the data generated with 230 human Affymetrix U133A gene chips indicated that the co-regulated expression of CMP-SA and GDP-fuc transporters was not common. Taken together our results suggest that inflammation-induced transcriptional regulation exists for Golgi membrane transporters required for the synthesis of the inflammation-inducible zip code sulfo sLex glycans.
Revised July 12, 2004
Accepted July 14, 2004
ORIGINAL ARTICLES
Inflammation-induced transcriptional regulation of Golgi transporters required for the synthesis of sulfo sLex glycan epitopes
2 MediCel, Haartmaninkatu 8, FIN-00290 Helsinki, Finland
3 Rational Drug Design Program, Department of Bacteriology and Immunology, Haartman Institute and Biomedicum, P.O. Box 63, FIN-00014 University of Helsinki, Finland
4 Department of Developmental Biology, Tampere University Medical School, Fin-33101 Tampere, Finland; Department of Pathology, Tampere University Hospital, Fin-33101 Tampere, Finland
5 Rational Drug Design Program, Department of Bacteriology and Immunology, Haartman Institute and Biomedicum, P.O. Box 63, FIN-00014 University of Helsinki, Finland; HUCH Laboratory Diagnostics, Helsinki University Central Hospital, P.O. Box 401, FIN-00029 HUCH, Helsinki, Finland
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