Lowered expression of heparan sulfate/heparin biosynthesis enzyme N-deacetylase/N-sulfotransferase 1 results in increased sulfation of mast cell heparin
| Autor: | Katarina Holmborn, Magnus Åbrink, Lena Kjellén, Anders Dagälv |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Enzyme complex
Sulfotransferase Golgi Apparatus Glycobiology and Extracellular Matrices Biology Models Biological Biochemistry Amidohydrolases chemistry.chemical_compound Mice Sulfation medicine Animals Chondroitin sulfate Mast Cells Molecular Biology Cells Cultured Embryonic Stem Cells Heparan Sulfate Biosynthesis Mice Knockout Heparin Heparan sulfate Cell Biology Mast cell Embryo Mammalian Molecular biology carbohydrates (lipids) medicine.anatomical_structure chemistry Additions and Corrections Heparitin Sulfate Sulfotransferases medicine.drug Peptide Hydrolases |
| Zdroj: | Journal of Biological Chemistry. 287:11282 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.a111.303891 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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