Up-regulation of ceramide glucosyltransferase during the differentiation of U937 cells

J Biochem. 2011 Sep;150(3):303-10. doi: 10.1093/jb/mvr058. Epub 2011 May 10.

Abstract

The phorbol ester tetradecanoylphorbol acetate (TPA) induces promyelocytic leukaemia cells to differentiate to macrophage-like cells in vitro. During the course of this differentiation, the cells adhere to the bottom of the culture dish, a process that requires an increase in cell surface glycosphingolipids (GSLs). We examined the cellular content of glucosylceramide (GlcCer), the simplest of the GSLs, in a TPA-treated leukaemia cell line, U937. Following TPA treatment, we observed a 3.5-fold increase in GlcCer levels that was caused by enhanced activity of ceramide glucosyltransferase (GlcT-1), which catalyses ceramide glycosylation. Furthermore, in TPA-treated cell GlcT-1 amounts were increased at both the mRNA and protein levels. We also found decreased activity of lactosylceramide synthase in TPA-treated cells, which could also contribute to the increase in cellular GlcCer content.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Galactosyltransferases / metabolism
  • Glucosylceramides / metabolism*
  • Glucosyltransferases / metabolism*
  • Humans
  • Leukemia / enzymology
  • Leukemia / pathology
  • Macrophages / pathology
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • U937 Cells

Substances

  • Glucosylceramides
  • RNA, Messenger
  • Galactosyltransferases
  • Glucosyltransferases
  • UDPgalactose-glucosylceramide galactosyltransferase
  • ceramide glucosyltransferase
  • Tetradecanoylphorbol Acetate