Molecular cloning of Chinese hamster ceramide glucosyltransferase and its enhanced expression in peroxisome-defective mutant Z65 cells

Arch Biochem Biophys. 2002 Jul 15;403(2):171-8. doi: 10.1016/s0003-9861(02)00216-3.

Abstract

To clarify the metabolic bases of characteristic increases in the concentrations of glucosylceramide (CMH) and GM3 in peroxisome-defective mutant Chinese hamster ovary (CHO) cells (Z65), we measured the ceramide glucosyltransferase (CGT) and beta-glucosidase activities in Z65 and CHO-K1 cells, and found that the former enzyme was responsible for the accumulation of CMH in Z65 cells. Inhibition of CGT by D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) caused a marked reduction in a incorporation of [3-14C]serine to CMH in both CHO-K1 and Z65 cells, but resulted in the accumulation of ceramide in Z65 cells in a concentration higher than that in CHO-K1 cells. Then, we cloned the cDNA encoding CGT from CHO-K1 cells, which exhibited sequence homology with the human gene product (98.7%). Northern blot analysis of CGT revealed increased expression of it in Z65 cells compared with that in CHO-K1 cells, which probably caused the simultaneous increase in GM3. With an immunohistochemical procedure, GM3 was found to be more strongly expressed in the cell membrane of Z65 cells than in CHO-K1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • Enzyme Inhibitors / pharmacology
  • G(M3) Ganglioside / immunology
  • G(M3) Ganglioside / metabolism
  • Glucosyltransferases / antagonists & inhibitors
  • Glucosyltransferases / genetics*
  • Glucosyltransferases / metabolism*
  • Molecular Sequence Data
  • Morpholines / pharmacology
  • Mutation
  • Peroxisomes / genetics*
  • Peroxisomes / metabolism
  • Sphingolipids / biosynthesis
  • beta-Glucosidase / metabolism

Substances

  • Enzyme Inhibitors
  • G(M3) Ganglioside
  • Morpholines
  • Sphingolipids
  • RV 538
  • Glucosyltransferases
  • ceramide glucosyltransferase
  • beta-Glucosidase

Associated data

  • GENBANK/AF351131