title: Alteration of mannose transport in fibroblasts from type I carbohydrate deficient glycoprotein syndrome patients.
abstract: The aim of the present study was to explore how mannose enters fibroblasts derived from a panel of children suffering from different subtypes of type I carbohydrate deficient glycoprotein syndrome: seven carbohydrate deficient glycoprotein syndrome subtype Ia (phosphomannomutase deficiency), two carbohydrate deficient glycoprotein syndrome subtype Ib (phosphomannose isomerase deficiency) and two carbohydrate deficient glycoprotein syndrome subtype Ix (not identified deficiency). We showed that a specific mannose transport system exists in all the cells tested but has different characteristics with respect to carbohydrate deficient glycoprotein syndrome subtypes. Subtype Ia fibroblasts presented a mannose uptake equivalent or higher (maximum 1.6-fold) than control cells with a D-[2-3H]-mannose incorporation in nascent N-glycoproteins decreased up to 7-fold. Compared to control cells, the mannose uptake was greatly stimulated in subtype Ib (4.0-fold), due to lower Kuptake and higher Vmax values. Subtype Ib cells showed an increased incorporation of D-[2-3H]-mannose into nascent N-glycoproteins. Subtype Ix fibroblasts presented an intermediary status with mannose uptake equivalent to the control but with an increased incorporation of D-[2-3H]-mannose in nascent N-glycoproteins. All together, our results demonstrate quantitative and/or qualitative modifications in mannose transport of all carbohydrate deficient glycoprotein syndrome fibroblasts in comparison to control cells, with a relative homogeneity within a considered subtype of carbohydrate deficient glycoprotein syndrome. These results are consistent with the possible use of mannose as a therapeutic agent in carbohydrate deficient glycoprotein syndrome Ib and Ix.
authors: Laboratoire de Biochimie A, Hôpital Bichat, 75877, Paris Cedex 18, France.labo.bioa@bch.ap-hop-paris.fr
authors: T
authors: T
authors: Dupre
authors: E
authors: E
authors: Ogier-Denis
authors: S E
authors: SE
authors: Moore
authors: V
authors: V
authors: Cormier-Daire
authors: M
authors: M
authors: Dehoux
authors: G
authors: G
authors: Durand
authors: N
authors: N
authors: Seta
authors: P
authors: P
authors: Codogno
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D018981:Congenital Disorders of Glycosylation / Q000188:drug therapy / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008358:Mannose / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D008358:Mannose