Nitric oxide degradation of heparin and heparan sulphate

Vilar, Rolando; Ghael, Dineshchandra; Li, Min; Bhagat, Devan D.; Arrigo, L; Cowman, Mary K.; Dweck, Harry S.; Rosenfeld, Louis

doi:10.1042/bj3240473

Cited by 68 publications

(49 citation statements)

References 47 publications

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“…Nitrite can be derived from cellular NO under physiological conditions (20), but also NO gas can be used to degrade HS (21). The results of our studies show that when purified S-nitrosylated Gpc-1 substituted with GlcNH 3 ϩ -rich HS chains is exposed in vitro to a reducing agent such as ascorbate, NO is released.…”

mentioning

confidence: 49%

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Belting

Mani

Jönsson

et al. 2003

Journal of Biological Chemistry

151

113

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Polyamines (putrescine, spermidine, and spermine) are essential for growth and survival of all cells. When polyamine biosynthesis is inhibited, there is up-regulation of import. The mammalian polyamine transport system is unknown. We have previously shown that the heparan sulfate (HS) side chains of recycling glypican-1 (Gpc-1) can sequester spermine, that intracellular polyamine depletion increases the number of NO-sensitive N-unsubstituted glucosamines in HS, and that NO-dependent cleavage of HS at these sites is required for spermine uptake. The NO is derived from S-nitroso groups in the Gpc-1 protein. Using RNA interference technology as well as biochemical and microscopic techniques applied to both normal and uptake-deficient cells, we demonstrate that inhibition of Gpc-1 expression abrogates spermine uptake and intracellular delivery. In unperturbed cells, spermine and recycling Gpc-1 carrying HS chains rich in Nunsubstituted glucosamines were co-localized. By exposing cells to ascorbate, we induced release of NO from the S-nitroso groups, resulting in HS degradation and unloading of the sequestered polyamines as well as nuclear targeting of the deglycanated Gpc-1 protein. Polyamine uptake-deficient cells appear to have a defect in the NO release mechanism. We have managed to restore spermine uptake partially in these cells by providing spermine NONOate and ascorbate. The former bound to the HS chains of recycling Gpc-1 and S-nitrosylated the core protein. Ascorbate released NO, which degraded HS and liberated the bound spermine. Recycling HS proteoglycans of the glypican-type may be plasma membrane carriers for cargo taken up by caveolar endocytosis.

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mentioning

confidence: 49%

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Belting

Mani

Jönsson

et al. 2003

Journal of Biological Chemistry

151

113

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“…Thus far, only NO, nitrous acid, S-nitrosothiols, and peroxynitrite have been shown to be capable of degrading carbohydrate polymers (9,10,12). Specifically, these RNSs degrade heparin, heparan sulfate, and chondroitin sulfate through a common deaminative mechanism (9,10). In contrast, peroxynitrite selectively degrades hyaluronic acid and chondroitin sulfate but not heparin (12) and degrades carbohydrate polymers via an unidentified mechanism thought to resemble chemical depolymerization by free hydroxyl radical attack.…”

Section: Degradation Of Carbohydrates Within Apc Endosomes By Reactivementioning

confidence: 99%

“…We next asked which RNSs can chemically degrade PSA. Thus far, only NO, nitrous acid, S-nitrosothiols, and peroxynitrite have been shown to be capable of degrading carbohydrate polymers (9,10,12). Specifically, these RNSs degrade heparin, heparan sulfate, and chondroitin sulfate through a common deaminative mechanism (9,10).…”

Section: Degradation Of Carbohydrates Within Apc Endosomes By Reactivementioning

confidence: 99%

Microbial carbohydrate depolymerization by antigen-presenting cells: Deamination prior to presentation by the MHCII pathway

Duan

Avci

Kasper

2008

Proc. Natl. Acad. Sci. U.S.A.

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After uptake by the endosome of an antigen-presenting cell (APC), exogenous proteins are known to be degraded into peptides by protease digestion. Here, we report the mechanism by which pure carbohydrates can be depolymerized within APC endosomes/lysosomes by nitric oxide (NO)-derived reactive nitrogen species (RNSs) and/or superoxide-derived reactive oxygen species (ROSs). Earlier studies showed that depolymerization of polysaccharide A (PSA) from Bacteroides fragilis in the endosome depends on the APC's having an intact inducible nitric oxide synthase (iNOS) gene; the chemical mechanism underlying depolymerization of a carbohydrate within the endosome/lysosome is described here. Examining the ability of the major RNSs to degrade PSA, we determined that deamination is the predominant mechanism for PSA processing in APCs and is a required step in PSA presentation to antigen processing ͉ MHC class II ͉ reactive nitrogen species

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“…In this case, NO ϩ ought to be the reactive species. Also NO gas (53) and acidified NO species derived from SNO-glutathione (54) can cleave HS and heparin quite extensively at these units. If NO ϩ is the reactive species in HNO 2 at pH 1.5 (52), this may explain why GlcNH 3 ϩ residues are resistant under these conditions (50).…”

Section: Figmentioning

confidence: 99%

Prion, Amyloid β-derived Cu(II) Ions, or Free Zn(II) Ions Support S-Nitroso-dependent Autocleavage of Glypican-1 Heparan Sulfate

Mani

Cheng

Havsmark

et al. 2003

Journal of Biological Chemistry

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Copper are generally bound to proteins, e.g. the prion and the amyloid ␤ proteins. We have previously shown that copper ions are required to nitrosylate thiol groups in the core protein of glypican-1, a heparan sulfate-substituted proteoglycan. When S-nitrosylated glypican-1 is then exposed to an appropriate reducing agent, such as ascorbate, nitric oxide is released and autocatalyzes deaminative cleavage of the glypican-1 heparan sulfate side chains at sites where the glucosamines are N-unsubstituted. These processes take place in a stepwise manner, whereas glypican-1 recycles via a caveolin-1-associated pathway where copper ions could be provided by the prion protein. Here we show, by using both biochemical and microscopic techniques, that (a) the glypican-1 core protein binds copper(II) ions, reduces them to copper(I) when the thiols are nitrosylated and reoxidizes copper(I) to copper(II) when ascorbate releases nitric oxide; (b) maximally S-nitrosylated glypican-1 can cleave its own heparan sulfate chains at all available sites in a nitroxyl ion-dependent reaction; (c) free zinc(II) ions, which are redox inert, also support autocleavage of glypican-1 heparan sulfate, probably via transnitrosation, whereas they inhibit copper(II)-supported degradation; and (d) copper(II)-loaded but not zinc(II)-loaded prion protein or amyloid ␤ peptide support heparan sulfate degradation. As glypican-1 in prion null cells is poorly S-nitrosylated and as ectopic expression of cellular prion protein restores S-nitrosylation of glypican-1 in these cells, we propose that one function of the cellular prion protein is to deliver copper(II) for the S-nitrosylation of recycling glypican-1.

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Nitric oxide degradation of heparin and heparan sulphate

Cited by 68 publications

References 47 publications

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Microbial carbohydrate depolymerization by antigen-presenting cells: Deamination prior to presentation by the MHCII pathway

Prion, Amyloid β-derived Cu(II) Ions, or Free Zn(II) Ions Support S-Nitroso-dependent Autocleavage of Glypican-1 Heparan Sulfate

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