Expression and regulation of glycosyltransferases for N-glycosyl oligosaccharides in fresh human surgical and murine tissues and cultured cell lines

M. Li, V. Andersen, P. Lance

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

1. Mammalian membrane and serum proteins are glycosylated by the addition of heterogeneous N-linked oligosaccharides. It has been widely speculated that oligosaccharide diversity is achieved by corresponding heterogeneity of expression of the glycosyltransferases that are responsible for oligosaccharide synthesis. 2. We surveyed mRNA levels of three sequentially acting glycosyltransferases, N-acetylglucosaminyltransferase I, β1,4-galactosyltransferase and α2,6-sialyltransferase, in 11 human tissues and confirmed the expected variations. 3. The size heterogeneity of α2,6-sialyltransferase transcripts reported in rat tissues was evident neither in the human tissue survey nor in a panel of murine RNAs. Tissue distributions of alternative terminal sialyltransferases, α2,6-sialyltransferase and α2,3-sialyltransferase, were distinct. 4. Relative glycosyltransferase mRNA levels in four transformed human cell lines cultured in vitro did not fully reflect levels in the corresponding human tissues. 5. Expression of α2,6-sialyltransferase mRNA was approximately 2.6-fold greater in adenocarcinomatous than in normal human colon, and β1,4-galactosyltransferase expression was approximately 1.8-fold greater in normal than in adenocarcinomatous colon. 6. n-Butyrate (0.003-0.005 mol/l), a short-chain fatty acid that is produced by colonic bacterial fermentation, caused approximately 80% inhibition of α2,6-sialyltransferase, approximately 2.5-fold induction of β1,4-galactosyltransferase and approximately 6-fold induction of N-acetylglucosaminyltransferase mRNAs in T84 (colonic) cells. The effects on α2,6-sialyltransferase and β1,4-galactosyltransferase were near maximal by 6 h, but induction of N-acetylglucosaminyltransferase was fully apparent only after exposure for 24 h.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalClinical Science
Volume89
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • Butyrates
  • Colonic neoplasms
  • Galactosyltransferases
  • Glycosyltransferases
  • N-acetylglucosaminyltransferases
  • Sialyltransferases

ASJC Scopus subject areas

  • Medicine(all)

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