Processing of macromolecular heparin by heparanase

摘要: Heparanase is an endo-glucuronidase expressed in a variety of tissues and cells that selectively cleaves extracellular cell-surface heparan sulfate. Here we propose this enzyme involved also the processing serglycin heparin proteoglycan mouse mast cells. In process, newly synthesized chains (60-100 kDa) are degraded to fragments (10-20 similar size commercially available (Jacobsson, K. G., Lindahl, U. (1987) Biochem. J. 246, 409-415). A fraction these contains specific pentasaccharide sequence required for high affinity binding antithrombin implicated with anticoagulant activity. Rat skin heparin, which escapes vivo, was used as substrate reaction recombinant human heparanase. An incubation product commercial retained sequence, although oligosaccharides (3-4 containing could be by same enzyme. Commercial found powerful inhibitor (I50 approximately 20 nM disaccharide unit, 0.7 polysaccharide) heparanase action toward antithrombin-binding oligosaccharides. Cells derived from serglycin-processing mastocytoma protein highly other mammalian heparanases. These findings strongly suggest intracellular polysaccharide catalyzed heparanase, primarily target structures distinct sequence.