Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans

Panasyuk, Andrei; Frati, Elene; Ribault, Didier; Mitrović, D

doi:10.1016/0891-5849(94)90139-2

Cited by 62 publications

(36 citation statements)

References 24 publications

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“…The release of ROS leads to proteinuria by affecting glomerular endothelial and epithelial cells and disturbing normal glomerular permselectivity [155,156], most likely by degradation of GBM-associated heparan sulfate [3,28,157]. The susceptibility of different GAGs to depolymerization by ROS dependents on the degree of sulfation; low-or nonsulfated GAGs are more sensitive to depolymerization than high-sulfated GAGs [157][158][159]. Although changes in heparan sulfate during inflammation (and other pathologic processes in the kidney) may be very dynamically, pinpointing to specific changes of heparan sulfate may give clues for the development of therapeutic heparin or heparan sulfate preparations, which we will address in the next two paragraphs.…”

Section: Leukocyte Transmigration and Hspgsmentioning

confidence: 99%

Heparan sulfate proteoglycans in glomerular inflammation

Rops

Vlag

Lensen

et al. 2004

Kidney International

113

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Heparan sulfate proteoglycans (HSPGs) are glycoproteins consisting of a core protein to which linear heparan sulfate side chains are covalently attached. These heparan sulfate side chains can be modified at different positions by several enzymes, which include N-deacetylases, N- and O-sulfotransferases, and an epimerase. These heparan sulfate modifications give rise to an enormous structural diversity, which corresponds to the variety of biologic functions mediated by heparan sulfate, including its role in inflammation. The HSPGs in the glomerular basement membrane (GBM), perlecan, agrin, and collagen XVIII, play an important role in the charge-selective permeability of the glomerular filter. In addition to these HSPGs, various cell types express HSPGs at their cell surface, which include syndecans, glypicans, CD44, and betaglycan. During inflammation, HSPGs, especially heparan sulfate, in the extracellular matrix (ECM) and at the surface of endothelial cells bind chemokines, which establishes a local concentration gradient recruiting leukocytes. Endothelial and leukocyte cell surface HSPGs also play a role in their direct adhesive interactions via other cell surface adhesion molecules, such as selectins and beta2 integrin. Activated leukocytes and endothelial cells exert heparanase activity, resulting in degradation of heparan sulfate moieties in the ECM, which facilitates leukocyte passage into tissues and the release of heparan sulfate-bound factors. In various renal inflammatory diseases the expression of agrin and GBM-associated heparan sulfate is decreased, while the expression of CD44 is increased. Heparan sulfate or heparin preparations affect inflammatory cell behavior and have promising therapeutic, anti-inflammatory properties by preventing leukocyte adhesion/influx and tissue damage.

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Section: Leukocyte Transmigration and Hspgsmentioning

confidence: 99%

Heparan sulfate proteoglycans in glomerular inflammation

Rops

Vlag

Lensen

et al. 2004

Kidney International

113

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“…It is supposed that this observation might be a result of HSPGs cleavage by heparanase (Maxhimer et al 2005). Moreover, decreased HSPGs sulfation, induced by hyperglycemia, makes HSPGs more susceptible to degradation (Kashihara et al 1992;Moseley et al 1995;Panasyuk et al 1994;Rops et al 2004).…”

Section: Diabetes Mellitusmentioning

confidence: 99%

The Role of Heparanase in Diseases of the Glomeruli

Szymczak

Kuźniar

Klinger

2010

Arch. Immunol. Ther. Exp.

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The glomerular basement membrane (GBM) is a kind of net that remains in a state of dynamic equilibrium. Heparan sulfate proteoglycans (HSPGs) are among its most important components. There are much data indicating the significance of these proteoglycans in protecting proteins such as albumins from penetrating to the urine, although some new data indicate that loss of proteoglycans does not always lead to proteinuria. Heparanase is an enzyme which cleaves beta 1,4 D: -glucuronic bonds in sugar groups of HSPGs. Thus it is supposed that heparanase may have an important role in the pathogenesis of proteinuria. Increased heparanase expression and activity in the course of many glomerular diseases was observed. The most widely documented is the significance of heparanase in the pathogenesis of diabetic nephropathy. Moreover, heparanase acts as a signaling molecule and may influence the concentrations of active growth factors in the GBM. It is being investigated whether heparanase inhibition may cause decreased proteinuria. The heparanase inhibitor PI-88 (phosphomannopentaose sulfate) was effective as an antiproteinuric drug in an experimental model of membranous nephropathy. Nevertheless, this drug is burdened by some toxicity, so further investigations should be considered.

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“…Previous reports have shown that reactive oxygen species (ROS) are able to degrade proteoglycan core proteins (17,18) and glycosaminoglycans including HS and heparin (19 -23) or can inhibit de novo synthesis of proteoglycans (17,24). Furthermore, ROS were demonstrated to be involved in experimental glomerulopathies such as Adriamycin (ADR) nephropathy (25), puromycin aminonucleoside nephrosis (26), passive Heymann nephritis (27), and anti-GBM nephritis (28).…”

Section: Heparan Sulfate (Hs)mentioning

confidence: 99%

Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

Raats

Bakker

Born

et al. 1997

Journal of Biological Chemistry

105

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Heparan sulfate, the polysaccharide side chain of heparan sulfate proteoglycan, is important for the permselective properties of the glomerular basement membrane. In this report, we show a role for hydroxyl radicals in heparan sulfate degradation and an enhanced glomerular basement membrane permeability. First, in enzyme-linked immunosorbent assay, exposure of coated heparan sulfate (proteoglycan) to reactive oxygen species resulted in a ؎50% decrease of binding of a monoclonal antibody against heparan sulfate, whereas binding of an antibody against the core protein remained unaltered. Second, on polyacrylamide gel electrophoresis, the molecular weight of heparan sulfate exposed to radicals was reduced which indicates depolymerization. Both in enzyme-linked immunosorbent assay and gel electrophoresis, hydroxyl radicals are instrumental for heparan sulfate degradation as shown by the addition of various radical scavengers. Third, in an experimental model for human nephrotic syndrome (Adriamycin nephropathy in rats), glomerular basement membrane staining of two recently described anti-heparan sulfate antibodies (JM403 and KJ865) was reduced by 24 and 43%. Treatment of Adriamycin-exposed rats with the hydroxyl radical scavenger dimethylthiourea both reduced albuminuria by 37% (p < 0.01) and partly prevented loss of heparan sulfate staining by 53% (JM403) and 39% (KJ865) (p < 0.03). In contrast to the heparan sulfate side chains, the core protein expression and the extent of glycanation did not change in Adriamycin nephropathy. We conclude that glomerular basement membrane heparan sulfate is susceptible to depolymerization by hydroxyl radicals leading to loss of glomerular basement membrane integrity and albuminuria.Heparan sulfate (HS) 1 is the anionic polysaccharide side chain of heparan sulfate proteoglycan (HSPG) present in basement membranes, extracellular matrix, and on the cell surface of many (if not all) cell types (1-3). Several investigators have shown that HS plays an important role in the permselective properties of the glomerular basement membrane (GBM) (4, 5). Enzymatic digestion of HS by heparitinase resulted in an increased passage of native ferritin and albumin through the GBM (6, 7). Furthermore, intravenous injection of a monoclonal antibody (mAb) directed against HS induces acute, selective proteinuria in rats (8). A reduction in GBM HS-associated anionic sites was found with cationic probes in several human and experimental proteinuric glomerulopathies (9, 10). With recently developed antibodies directed against GBM HSPG core protein and the HS side chain (11, 12), we demonstrated a decrease in HS staining in the GBM in different human proteinuric glomerulopathies, whereas the staining of the HSPG core protein remained unaltered (13). The mechanism responsible for this observation remains to be elucidated. In lupus nephritis, masking of HS by autoantibodies complexed to nucleosomes is proposed as a mechanism for the decrease in HS staining and albuminuria (14). In human and experimental diabe...

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Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans

Cited by 62 publications

References 24 publications

Heparan sulfate proteoglycans in glomerular inflammation

Heparan sulfate proteoglycans in glomerular inflammation

The Role of Heparanase in Diseases of the Glomeruli

Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

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