Inflammation-induced transcriptional regulation of Golgi transporters required for the synthesis of sulfo sLex glycan epitopes.
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 SA, Fuc, 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 on inflammatory stimuli. Here we analyze the transcriptional coregulation 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. With in silico analysis, the data generated with 230 human Affymetrix U133A gene chips indicated that the coregulated 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.
Huopaniemi
Laura
L
Rational Drug Design Program, Department of Bacteriology and Immunology, Haartman Institute and Biomedicum, P.O. Box 63, FIN-00014 University of Helsinki, Finland.
Kolmer
Meelis
M
Niittymäki
Jaana
J
Pelto-Huikko
Markku
M
Renkonen
Risto
R
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000378:metabolism; D000939:Epitopes / Q000096:biosynthesis* / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism*; D006154:Guanosine Diphosphate Fucose / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000235:genetics; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D014158:Transcription, Genetic / Q000502:physiology*
C086949:6'-sulfated sialyl Lewis x; D002352:Carrier Proteins; D000939:Epitopes; D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D006154:Guanosine Diphosphate Fucose; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D010724:Phosphoadenosine Phosphosulfate