Intracellular inhibition of blood group A glycosyltransferase

Eur J Biochem. 2000 Aug;267(15):4840-9. doi: 10.1046/j.1432-1327.2000.01544.x.

Abstract

We report the intracellular inhibition of blood group A N-acetylgalactosaminyltransferase in the human colorectal carcinoma cell line HT29 by 3-amino-3-deoxy-[Fucalpha(1-2)]Galbeta-O(CH2)7CH3. Inhibition was demonstrated with a novel capillary electrophoresis assay that monitored decreased intracellular conversion of fluorescently labelled Fucalpha(1-2)Gal-R acceptor to the corresponding A epitope, GalNAcalpha(1-3)[Fucalpha(1-2)]Galbeta-R. Growth of HT29 cells with either the amino-inhibitor or a competitive substrate, Fucalpha(1-2)Galbeta-O(CH2)7CH3, also resulted in decreased expression of blood group A determinants on cell-associated glycoproteins, as detected by immunoprecipitation analysis using A-specific monoclonal antibodies. Furthermore, exposure of these cells to the amino-inhibitor or competitive substrate resulted in significant reduction of cell-surface expression of blood group A determinants. As integrin alpha3beta1, a cell-surface receptor mediating cell-cell and cell-extracellular matrix interactions, was shown previously to be a major carrier of blood group A determinants on HT29 cells, the studies described herein highlight the potential usefulness of these compounds for elucidating the role of blood group A determinants in biological phenomena.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Disaccharides / pharmacology
  • Electrophoresis, Capillary / methods*
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Flow Cytometry
  • Humans
  • Kinetics
  • Models, Chemical
  • N-Acetylgalactosaminyltransferases / antagonists & inhibitors*
  • N-Acetylgalactosaminyltransferases / biosynthesis
  • N-Acetylgalactosaminyltransferases / chemistry
  • Oligosaccharides / pharmacology
  • Precipitin Tests
  • Serum Albumin, Bovine / metabolism
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Disaccharides
  • Epitopes
  • Oligosaccharides
  • Serum Albumin, Bovine
  • N-Acetylgalactosaminyltransferases
  • UDPgalactosamine-galactose acetylgalactosaminyltransferase