title: Lowered expression of heparan sulfate/heparin biosynthesis enzyme N-deacetylase/n-sulfotransferase 1 results in increased sulfation of mast cell heparin.
abstract: Deficiency of the heparan sulfate biosynthesis enzyme N-deacetylase/N-sulfotransferase 1 (NDST1) in mice causes severely disturbed heparan sulfate biosynthesis in all organs, whereas lack of NDST2 only affects heparin biosynthesis in mast cells (MCs). To investigate the individual and combined roles of NDST1 and NDST2 during MC development, in vitro differentiated MCs derived from mouse embryos and embryonic stem cells, respectively, have been studied. Whereas MC development will not occur in the absence of both NDST1 and NDST2, lack of NDST2 alone results in the generation of defective MCs. Surprisingly, the relative amount of heparin produced in NDST1(+/-) and NDST1(-/-) MCs is higher (≈30%) than in control MCs where ≈95% of the (35)S-labeled glycosaminoglycans produced is chondroitin sulfate. Lowered expression of NDST1 also results in a higher sulfate content of the heparin synthesized and is accompanied by increased levels of stored MC proteases. A model of the GAGosome, a hypothetical Golgi enzyme complex, is used to explain the results.
authors: Department of Medical Biochemistry and Microbiology, Uppsala University, and Biomedical Sciences and Veterinary Public Health, SLU, SE-751 23 Uppsala, Sweden.
authors: Anders
authors: A
authors: Dagälv
authors: Katarina
authors: K
authors: Holmborn
authors: Lena
authors: L
authors: Kjellén
authors: Magnus
authors: M
authors: Abrink
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology / Q000235:genetics; D006493:Heparin / Q000096:biosynthesis* / Q000235:genetics; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000581:Amidohydrolases; D006493:Heparin; D006497:Heparan Sulfate; D010447:Peptide Hydrolases; D015238:Sulfotransferases; C491855:Ndst2 protein, mouse; C021350:heparitin sulfotransferase