title: Defect of N-glycosylation is not directly related to congenital disorder of glycosylation Ia fibroblast sensitivity to staurosporine-induced cell death.
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.
authors.affiliation: INSERM Unité 504, Bâtiment INSERM, 94807 Villejuif Cedex, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Lavieu
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Frénoy
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Joëlle
authors.initials: J
authors.lastname: Botti
mesh_terms: D000483:Alleles; D017209:Apoptosis; D015153:Blotting, Western; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005808:Genes, Recessive; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000494:pharmacology; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics; D011134:Polysaccharides / Q000737:chemistry; D012680:Sensitivity and Specificity; D019311:Staurosporine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D011134:Polysaccharides; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase; D019311:Staurosporine; D008358:Mannose