title: Receptor-mediated selective impairment of insulin-like growth factor-1 activity in congenital disorders of glycosylation patients.
abstract: Congenital disorders of glycosylation (CDG) patients share a basic feature of protein hypoglycosylation. Activity of growth factors and their receptors, glycoproteins playing a pivotal role during child development, remains unexplored in CDG patients.
  
  
  
  Peripheral blood lymphocytes (PBL) isolated from 9 CDG patients and 12 healthy controls were cultured in the presence of fetal bovine serum (FBS), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1), and BrdU incorporation was measured. Levels of plasma IGF-1 and PBL IGF-1 receptor (IGF-1R) and its glycosylation were detected using immunoassay and western blot.
  
  
  
  CDG patients showed significantly less (P < 0.01) serum-induced 5'-Bromo-2'-deoxyuridine (BrdU) incorporation in PBL than in controls. PDGF-/FGF-stimulated BrdU incorporation showed no difference in patients and controls, whereas IGF-1-induced DNA synthesis was significantly (P < 0.01) less in patients. Plasma IGF-1 levels and PBL IGF-1 receptor protein were significantly (P < 0.01) reduced in patients as compared to controls. IGF-1 receptor in PBL of all CDG patients had significantly (P < 0.01) reduced carbohydrate content when compared with control.
  
  
  
  These results show selective impairment of IGF-1-induced DNA synthesis in lymphocytes of CDG patients through decreased gene expression and hypoglycosylation of the IGF-1 receptor.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait city, Kuwait.
authors.forename: Gursev S
authors.initials: GS
authors.lastname: Dhaunsi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002417:Cattle; D018981:Congenital Disorders of Glycosylation / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000097:blood
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C000597236:IGF1R protein, human; D010982:Platelet-Derived Growth Factor; D017451:Receptors, Somatomedin; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1