Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans

Bame, Karen J.

doi:10.1093/glycob/11.6.91r

Cited by 145 publications

(137 citation statements)

References 64 publications

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“…However, these heparan sulphate changes occur at the macroalbuminuric stage of diabetic nephropathy, since no glomerular heparan sulphate alterations were found at the microalbuminuric stage [15]. Recently, we showed that glomerular production of heparanase, an endo-β-1,4-D-glucuronidase involved in the hydrolytic cleavage of the β-1,4-glycosidic bond between glucuronic acid and glucosamine residues within N-sulphated and/or Nacetylated/N-sulphated domains of heparan sulphate [16,17], was increased in patients with overt diabetic nephropathy [11,18]. In addition, heparanase activity was detected in the urine of diabetic patients [19].…”

Section: Introductionmentioning

confidence: 94%

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

et al. 2007

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Aims/hypothesis Recent studies suggest that loss of heparan sulphate in the glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due to the increased production of heparanase, a heparan sulphate-degrading endoglycosidase. Our present study addresses whether heparan sulphate with different modifications is differentially reduced in the GBM and whether heparanase selectively cleaves heparan sulphate with different domain specificities. Methods The heparan sulphate content of renal biopsies (14 diabetic nephropathy, five normal) were analysed by immunofluorescence staining with four anti-heparan sulphate antibodies: JM403, a monoclonal antibody (mAb) recognising N-unsubstituted glucosamine residues; two phage displayderived single chain antibodies HS4C3 and EW3D10, defining sulphated heparan sulphate domains; and anti-K5 antibody, an mAb recognising unmodified heparan sulphate domains. Results We found that modified heparan sulphate domains (JM403, HS4C3 and EW3D10), but not unmodified domains (anti-K5) and agrin core protein were reduced in the GBM of kidneys from patients with diabetic nephropathy, compared with controls. Glomerular heparanase levels were increased in diabetic nephropathy kidneys and inversely correlated with the amounts of modified heparan sulphate domains. Increased heparanase production and loss of JM403 staining in the GBM Diabetologia (2008) 51:372-382

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Section: Introductionmentioning

confidence: 94%

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

et al. 2007

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“…44). Heparanase can be present both at the cell surface and in intracellular endosomal compartments.…”

Section: Suramin Treatment Causes Accumulation Of S-nitrosylatedmentioning

confidence: 99%

Nitric Oxide-dependent Processing of Heparan Sulfate in Recycling S-Nitrosylated Glypican-1 Takes Place in Caveolin-1-containing Endosomes

Cheng

Mani

Born

et al. 2002

Journal of Biological Chemistry

108

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However, such residues were scarce in cell surface glypican-1. Brefeldin A-arrested glypican-1, which was non-S-nitrosylated and carried side chains rich in Nunsubstituted glucosamines, colocalized extensively with caveolin-1 but not with Rab9. Suramin, which inhibits heparanase, induced the appearance of Snitrosylated glypican-1 in caveolin-1-rich compartments. Inhibition of deaminative cleavage did not prevent heparanase from generating heparan sulfate oligosaccharides that colocalized strongly with caveolin-1. Growthquiescent cells displayed extensive NO-dependent deaminative cleavage of heparan sulfate-generating anhydromannose-terminating fragments that were partly associated with acidic vesicles. Proliferating cells generated such fragments during polyamine uptake. We conclude that recycling glypican-1 that is associated with caveolin-1-containing endosomes undergoes sequential N-desulfation/N-deacetylation, heparanase cleavage, S-nitrosylation, NO release, and deaminative cleavage of its side chains in conjunction with polyamine uptake.Mammalian glypican-1 (Gpc-1) 1 is a member of a glycosylphosphatidylinositol (GPI)-linked cell-surface proteoglycan (PG) family with six known members to date. These PG, like other cell surface PG, are selective regulators of ligand-receptor encounters and thereby control growth and development (1-4). Gpc proteins are post-translationally modified by the addition of the glycosaminoglycan heparan sulfate (HS) at sites located close to the C-terminal GPI-membrane anchor (see Scheme 1). The central part of the protein consists of a cysteine-rich domain containing information that ensures a high level of HS substitution (5). Many of the functions of Gpc are dependent on the HS side chains, which are capable of binding and/or activating and/or transporting a variety of growth factors, cytokines, enzymes, viral proteins, and polyamines (6 -11).GPI-anchored proteins are usually associated with sphingolipid-and cholesterol-rich plasma membrane domains. Such enriched domains may exist either as small phase-separated "rafts" or, when associated with caveolin-1 (Cav-1), form flaskshaped plasmalemmal invaginations called caveolae, which are involved in signal transduction and special forms of non-clathrindependent endocytosis mediated by Cav-1-containing endosomes, also called caveosomes (12)(13)(14)(15)(16)(17).Biochemical studies using radioactively labeled precursors have demonstrated recycling of newly made Gpc-1 in normal fibroblasts as well as in transformed cells (18,19). During recycling, the HS side chains are degraded both by heparanase and by NO-dependent deaminative cleavage at N-unsubstituted glucosamine residues (GlcNH 3 ϩ ) (20). New HS chains can then be synthesized on the stubs remaining on the core protein (see Scheme 1). Biosynthesis of HS takes place in the Golgi and involves many interacting enzymes (21,22). The stubs should first be extended with a GlcNAc-hexuronic acid (HexUA) repeat backbone. The GlcNH 3 ϩ residues are either a result of inadequate sulfation dur...

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“…Heparan sulfate (HS) 3 is a structurally complex polysaccharide that is expressed ubiquitously on the cell surface and in the extracellular matrix. HS is composed of repeating disaccharide units of glucuronic acid (GlcUA) and glucosamine.…”

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confidence: 99%

Deciphering Mode of Action of Heparanase Using Structurally Defined Oligosaccharides

Peterson

Liu

2012

Journal of Biological Chemistry

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Background: Heparanase is involved in the pathology of many diseases. Results: Heparanase cleaves heparan sulfate (HS) oligosaccharides in either consecutive or gapped cleavage mode. Conclusion: The susceptibility of glycosidic linkage bonds to heparanase degradation is sensitive to the nonreducing end saccharide structure of the cleavage site. Significance: The results will help us to understand the pathophysiological effects of HS that arise from heparanase activity.

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Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans

Cited by 145 publications

References 64 publications

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

Nitric Oxide-dependent Processing of Heparan Sulfate in Recycling S-Nitrosylated Glypican-1 Takes Place in Caveolin-1-containing Endosomes

Deciphering Mode of Action of Heparanase Using Structurally Defined Oligosaccharides

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