Defect of N-glycosylation is not directly related to congenital disorder of glycosylation Ia fibroblast sensitivity to staurosporine-induced cell death

Pediatr Res. 2005 Aug;58(2):254-7. doi: 10.1203/01.PDR.0000169962.02462.C0.

Abstract

Congenital disorder of glycosylation Ia (CDGIa) is an autosomal recessive disease that is caused by mutations in the gene PMM2 encoding phosphomannomutase, an enzyme that synthesizes mannose-1-phosphate, an important intermediate for the N-glycan biosynthesis. Here, we investigated the susceptibility of CDGIa fibroblasts to cell death induction. CDGIa fibroblasts were more sensitive than control fibroblasts to staurosporine-induced apoptosis. Supplementation with mannose, which corrects N-glycosylation in CDGIa fibroblasts, did not abrogate their higher sensitivity to staurosporine. These results show that the sensitivity of CDGIa fibroblasts to apoptosis is not directly related to their defective N-glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Apoptosis
  • Blotting, Western
  • Carbohydrate Metabolism, Inborn Errors / genetics*
  • Carbohydrate Metabolism, Inborn Errors / metabolism
  • Cell Death
  • Cell Survival
  • Cells, Cultured
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism*
  • Genes, Recessive
  • Glycosylation*
  • Humans
  • Mannose / pharmacology
  • Phosphotransferases (Phosphomutases) / genetics
  • Polysaccharides / chemistry
  • Sensitivity and Specificity
  • Staurosporine / pharmacology*
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Polysaccharides
  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase
  • Staurosporine
  • Mannose