Peroxynitrous acid induces structural and functional modifications to basement membranes and its key component, laminin

Degendorfer, Georg; Chuang, Christine Y.; Hammer, Astrid; Malle, Ernst; Davies, Michael J.

doi:10.1016/j.freeradbiomed.2015.09.018

Cited by 41 publications

(48 citation statements)

References 54 publications

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“…5 shows MS fragmentation spectra of the native peptide, together with those for peptides with single oxidations (m/ z + 16; sulfoxide formation) at Met 2082 and Met 2084 , respectively. The + 16 Da mass shifts consistent with the addition of a single oxygen atom, are marked (dotted grey lines) for the diagnostic ions, y 9 for Met 2084 and b 2 for Met 2082 . The ions y 9 and y 10 contain only Met 2084 , and in the oxidised form, neutral loss of CH 3 SOH was observed for both ions (Fig.…”

Section: Oxidation Of Met Residues Can Results In Neutral Loss Of Methmentioning

confidence: 99%

“…Evidence has also been presented for ECM damage by other oxidants associated with both normal metabolism and inflammation, such as peroxynitrous acid, and for the presence of modified ECM species in human atherosclerotic lesions (e.g. [6,7,[9][10][11]72]). However the exact nature, sites and extents of modification induced by MPO and its oxidants (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The gels were developed under a constant voltage of 160 V for 70 min. Bands on the gels were detected using silver staining, as described previously [9], or by immunoblotting [9] using a rat monoclonal anti-mouse laminin antibody (clone AL-2 1:20000 dilution) with detection performed using a biotinylated anti-rat secondary antibody (1:5000 dilution) and streptavidin-conjugated HRP (1:1000 dilution), developed using an ECL reagent (Perkin Elmer, MA, USA) and imaged with a chemiluminescence imager (Syngene, MD, USA). The absorbance of each well at 405 nm was then read every 5 min over a 30 min period using a microplate reader.…”

Section: Analysis Of Structural Changes On Laminin Using Sds-page Witmentioning

confidence: 99%

“…Recent studies have shown that the ECM is highly susceptible to oxidative damage due to its high abundance, its low rate of turnover (which can results in accumulation of damage during ageing and disease) and the relatively low levels of extracellular antioxidant, repairs and catabolic systems [5][6][7]. Considerable data has been presented that demonstrates that oxidants generated by activated leukocytes (neutrophils, monocytes, tissue macrophages) can induce structural and functional changes to ECM proteins and proteoglycans (proteins with covalently attached GAGs), with damage evident in multiple tissue samples, including within human atherosclerotic lesions [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

Nybo

Deiterich

Gamon

et al. 2018

Free Radical Biology and Medicine

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A B S T R A C TBasement membranes are specialized extracellular matrices that underlie arterial wall endothelial cells, with laminin being a key structural and biologically-active component. Hypochlorous acid (HOCl), a potent oxidizing and chlorinating agent, is formed in vivo at sites of inflammation via the enzymatic action of myeloperoxidase (MPO), released by activated leukocytes. Considerable data supports a role for MPO-derived oxidants in cardiovascular disease and particularly atherosclerosis. These effects may be mediated via extracellular matrix damage to which MPO binds. Herein we detect and quantify sites of oxidation and chlorination on isolated laminin-111, and laminin in basement membrane extracts (BME), by use of mass spectrometry. Increased modification was detected with increasing oxidant exposure. Mass mapping indicated selectivity in the sites and extent of damage; Met residues were most heavily modified. Fewer modifications were detected with BME, possibly due to the shielding effects. HOCl oxidised 30 (of 56 total) Met and 7 (of 24) Trp residues, and chlorinated 33 (of 99) Tyr residues; 3 Tyr were dichlorinated. An additional 8 Met and 10 Trp oxidations, 14 chlorinations, and 18 dichlorinations were detected with the MPO/H 2 O 2 /Clsystem when compared to reagent HOCl. Interestingly, chlorination was detected at Tyr 2415 in the integrin-binding region; this may decrease cellular adhesion. Co-localization of MPO-damaged epitopes and laminin was detected in human atherosclerotic lesions. These data indicate that laminin is extensively modified by MPO-derived oxidants, with structural and functional changes. These modifications, and compromised cell-matrix interactions, may promote endothelial cell dysfunction, weaken the structure of atherosclerotic lesions, and enhance lesion rupture.

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Section: Oxidation Of Met Residues Can Results In Neutral Loss Of Methmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Structural Changes On Laminin Using Sds-page Witmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

Nybo

Deiterich

Gamon

et al. 2018

Free Radical Biology and Medicine

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“…to give nitrated products. 3-NitroTyr has been reported to be present at elevated levels in all grades of human atherosclerotic lesions and present on multiple proteins [46], including high-and low-density-lipoproteins [47], and the ECM materials perlecan [48], laminin [49] and fibronectin [50]. Furthermore, immunoglobulins against 3-nitroTyr epitopes have been detected in human atherosclerotic lesions and the circulation of subjects with coronary artery disease, linking oxidant production and activation of the immune system [51].…”

Section: Introductionmentioning

confidence: 99%

Exposure of tropoelastin to peroxynitrous acid gives high yields of nitrated tyrosine residues, di-tyrosine cross-links and altered protein structure and function

Degendorfer

Chuang

Mariotti

et al. 2018

Free Radical Biology and Medicine

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Elastin is an abundant extracellular matrix protein in elastic tissues, including the lungs, skin and arteries, and comprises 30-57% of the aorta by dry mass. The monomeric precursor, tropoelastin (TE), undergoes complex processing during elastogenesis to form mature elastic fibres. Peroxynitrous acid (ONOOH), a potent oxidising and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals. Considerable evidence supports ONOOH formation in the inflamed artery wall, and a role for this species in the development of human atherosclerotic lesions, with ONOOH-damaged extracellular matrix implicated in lesion rupture. We demonstrate that TE is highly sensitive to ONOOH, with this resulting in extensive dimerization, fragmentation and nitration of Tyr residues to give 3-nitrotyrosine (3-nitroTyr). This occurs with equimolar or greater levels of oxidant and increases in a dose-dependent manner. Quantification of Tyr loss and 3-nitroTyr formation indicates extensive Tyr modification with up to two modified Tyr per protein molecule, and up to 8% conversion of initial ONOOH to 3-nitroTyr. These effects were modulated by bicarbonate, an alternative target for ONOOH. Inter- and intra-protein di-tyrosine cross-links have been characterized by mass spectrometry. Examination of human atherosclerotic lesions shows colocalization of 3-nitroTyr with elastin epitopes, consistent with TE or elastin modification in vivo, and also an association of 3-nitroTyr containing proteins and elastin with lipid deposits. These data suggest that exposure of TE to ONOOH gives marked chemical and structural changes to TE and altered matrix assembly, and that such damage accumulates in human arterial tissue during the development of atherosclerosis.

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Rubus imperialis (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects

Tonin

Thiesen

Nunes

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and HO-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the HO-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.

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Peroxynitrous acid induces structural and functional modifications to basement membranes and its key component, laminin

Cited by 41 publications

References 54 publications

Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

Chlorination and oxidation of the extracellular matrix protein laminin and basement membrane extracts by hypochlorous acid and myeloperoxidase

Exposure of tropoelastin to peroxynitrous acid gives high yields of nitrated tyrosine residues, di-tyrosine cross-links and altered protein structure and function

Rubus imperialis (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects

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