The membrane of most cells in the body is surrounded by a dynamically regulated, highly-hydrated
fibrous meshwork of carbohydrates, known as pericellular matrix or glycocalyx. Its
main constituents are several glycoconjugates (see nomenclature and definitions in
Box 1), including glycolipids, the polysaccharide heparan sulfate (HS) linked to proteoglycan
core proteins (e.g. glypican, syndecan, betaglycan), the polysaccharide hyaluronan and proteins bound
to these polysaccharides.
Box 1
Nomenclature and definitions
Glycoconjugates: Various types of compounds consisting of carbohydrates covalently linked with other
types of chemical constituent.
Glycolipids: lipids with a carbohydrate attached by a covalent glycosidic bond. The carbohydrate
portion may be a single monosaccharide or a linear or branched chain.
Glycoproteins: proteins containing oligosaccharide chains (glycans) covalently attached to amino
acid side-chains; the carbohydrate portion consists of short chains, often branched.
Proteoglycans: proteins that are heavily glycosylated; the protein portion of the molecule represents
only a small portion of the total molecular weight; the carbohydrate portion consists
of long unbranched repeating disaccharide units (glycosaminoglycans, a.k.a. mucopolysaccharides).
The three major classes of proteoglycans, characterized by their side chains, are
the heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and keratan
sulfate proteoglycans.
Polysaccharides: polymeric carbohydrate molecules composed of relatively long chains of monosaccharide
units bound together by glycosidic linkages.
Lipopolysaccharides: large molecules consisting of a lipid and a polysaccharide composed of O-antigen,
outer core, and inner core joined by a covalent bond; they are typically found in
the outer membrane of Gram-negative BACTERIA. They are also known as lipoglycans and
endotoxins.
Peptidoglycans: polymers consisting of amino acids and specific sugars — alternating residues of
β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) — that form
a mesh-like layer outside the plasma membrane of most BACTERIA; they are also known
as mureins.
Keywords
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References
- Heparanase is required for activation and function of macrophages.Proc. Natl. Acad. Sci. U. S. A. 2016; 113: E7808-E7817
- Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase.Nature. 1984; 310: 241-244
- Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase.J. Biol. Chem. 1984; 259: 2283-2290
- Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes.J. Biol. Chem. 2013; 288: 10093-10099
- Opposing functions of heparanase-1 and heparanase-2 in cancer progression.Trends Biochem. Sci. 2018; 43: 18-31
- Heparanase: roles in cell survival, extracellular matrix remodelling and the development of kidney disease.Nat. Rev. Nephrol. 2017; 13: 201-212
- Structural characterization of human heparanase reveals insights into substrate recognition.Nat. Struct. Mol. Biol. 2015; 22: 1016-1022
- To NFkappaB or not to NFkappaB: the dilemma on how to inhibit a cancer cell fate regulator.Transl Med UniSa. 2012; 4: 73-85
- Heparanase activates the syndecan-syntenin-ALIX exosome pathway.Cell Res. 2015; 25: 412-428
- Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior.Matrix Biol. 2018; 65: 104-118
- Heparanase enhances tumor growth and chemoresistance by promoting autophagy.Cancer Res. 2015; 75: 3946-3957
- Cellular uptake of mammalian heparanase precursor involves low density lipoprotein receptor-related proteins, mannose 6-phosphate receptors, and heparan sulfate proteoglycans.J. Biol. Chem. 2005; 280: 33141-33148
- Processing and activation of latent heparanase occurs in lysosomes.J. Cell Sci. 2004; 117: 2249-2258
- The heparanase inhibitor PG545 is a potent anti-lymphoma drug: mode of action.Matrix Biol. 2018; (In press)https://doi.org/10.1016/j.matbio.2018.08.005
- Heparanase regulates thrombosis in vascular injury and stent-induced flow disturbance.J. Am. Coll. Cardiol. 2012; 59: 1551-1560
- Dual roles of heparanase in human carotid plaque calcification.Atherosclerosis. 2019; 283: 127-136
- Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca(2+) channels.Exp. Neurol. 2015; 274: 156-165
- Heparan sulfates support pyramidal cell excitability, synaptic plasticity, and context discrimination.Cerebr. Cortex. 2017; 27: 903-918
- Heparan sulfate and heparanase play key roles in mouse beta cell survival and autoimmune diabetes.J. Clin. Invest. 2012; 122: 132-141
- Heparanase is a host enzyme required for herpes simplex virus-1 release from cells.Nat. Commun. 2015; 6: 6985
Article info
Publication history
Published online: January 25, 2019
Accepted:
January 11,
2019
Received:
January 9,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
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- Dual roles of heparanase in human carotid plaque calcificationAtherosclerosisVol. 283
- PreviewCalcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity.
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