Myeloperoxidase and Horseradish Peroxidase Catalyze Tyrosine Nitration in Proteins from Nitrite and Hydrogen Peroxide

Sampson, Jacinda B.; Ye, Yaozu; Rosen, Henry; Beckman, Joseph S.

doi:10.1006/abbi.1998.0772

Cited by 306 publications

(188 citation statements)

References 51 publications

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“…Additional nitrating agents could be produced in alveoli by the reaction of HOCl (produced by the activity of MPO) with nitrite (the autoxidation product of NO . ), and by the enzymatic activity of MPO on ONOO -and nitrite [10,28,29]. This enzyme was present in its active form in BAL fluid and correlated with NTP concentrations in the present patients.…”

Section: Discussionsupporting

confidence: 62%

Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia

et al. 2000

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The study was designed to identify markers of oxidative injury, related to the nitric oxide derived cascade, in bronchoalveolar lavage (BAL) fluid from intensive care patients suspected of ventilator-associated pneumonia (VAP) and/or acute respiratory distress syndrome (ARDS).Thirty-eight patients developing VAP and/or ARDS (VAP/ARDS group) were compared to 20 ventilated patients without VAP/ARDS (control group). Myeloperoxidase (MPO) and elastase, taken as markers of neutrophil activation were measured by enzymatic techniques, and nitrated proteins (NTPs) by an immunological method. The cytotoxicity of the BAL fluid was tested using cultured human epithelial alveolar cells by the release of pre-incorporated 51 Cr.Mean NTP concentration and, MPO and elastase activities were different between the VAP/ARDS and control groups (p<0.05 for NTPs; p<0.005 for MPO; p<0.005 for elastase). NTP concentration correlated with MPO and elastase activity and neutrophil number (r=0.93, 0.91 and 0.87, respectively), but not to protein concentration and arterial oxygen tension/inspiratory oxygen fraction. The cytotoxicity of BAL correlated with NTP concentration (r=0.92) and MPO activity (r=0.89).It was concluded that the concentrations of nitrated proteins in bronchoalveolar lavage fluid correlated with the oxidant activity of neutrophils and that, bronchoalveolar lavage fluid cytotoxicity was correlated with the nitrated protein concentration and may be mediated by oxidants. Eur Respir J 2000; 16: 296±301. In patients with or at risk of acute lung injury or acute respiratory distress syndrome (ARDS), bronchoalveolar lavage (BAL) permits exploration of distal lung regions, which are mainly implicated in the inflammatory reaction and in acute respiratory failure. This bronchoscopy technique allows access to damaged tissues and gives the possibility of early detection of inflammatory mediators that have either accumulated or were produced in the lung. From studies already performed on BAL fluids, it appears that neutrophils constitute the majority of the cell population present in the lungs of ARDS patients, and that products of phagocyte degranulation such as myeloperoxidase (MPO) and elastase (free or complexed to a 1 -proteinase inhibitor) can also be found [1,2].These degranulation products argued in favour of activation of phagocytes in the lungs, involving release of reactive oxygen species, especially products derived from the activities of reduced nicotinamide adenine dinucleotide phoshate-oxidase and MPO: superoxide anion, hydrogen peroxide, and hypochlorous acid. Phagocytes also produce nitric oxide. The simultaneous production of NO . and O 2 . -allows in situ generation of peroxynitrite, a potent oxidative species which reacts quickly by incompletely determined mechanisms [3±5]. In the lung, ONOO -is reported to be responsible for alterations to surfactant of type II alveolar cells [6]. ONOO -is involved in the oxidation of lipoproteins, nucleic acids, proteins and peptides, and in the nitration of tyrosine an...

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Section: Discussionsupporting

confidence: 62%

Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia

et al. 2000

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“…3-NT is regarded as the "footprint" of ONOO Ϫ formation in vivo, 18 although other pathways of tyrosine nitration have been suggested. 32,33 Here, we for the first time present evidence that PGIS might be nitrated by ONOO Ϫ both in vitro and in vivo. Our previous studies have demonstrated that this enzyme undergoes tyrosine nitration by low concen- †PϽ0.05, C57BL6 vs hSOD-TG mice).…”

Section: Discussionmentioning

confidence: 73%

“…32,33 Our previous studies 20,21 demonstrated that ONOO Ϫ selectively nitrates tyrosine 450, a residue situated in the active site of PGIS. To assay whether CD40L inhibits PGIS by tyrosine nitration of the enzyme, PGIS proteins were first immunoprecipitated with a polyclonal antibody against PGIS and were further stained for a monoclonal antibody against 3-NT in Western blots.…”

Section: Davis and Zoumentioning

confidence: 99%

CD40 Ligand–Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo

Davis

Zou

2005

Circulation

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Background-Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand, CD40L, but the mechanisms and the mediators by which CD40L contributes to atherosclerosis are poorly defined. Here, we show how CD40L increases vascular inflammation and thrombosis via tyrosine nitration and inhibition of prostacyclin synthase (PGIS), an enzyme with antithrombotic, antiproliferative, and dilatory functions in the normal vasculature. Methods and Results-Exposure of cultured human aortic endothelial cells to clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently increased the production of superoxide (O 2 ⅐ Ϫ ), decreased nitric oxide (NO) bioactivity, and increased PGIS nitration. Furthermore, inhibition of CD40 expression by small interfering RNA blocked the effects of CD40L on O 2 ⅐ Ϫ , NO bioactivity, and PGIS nitration, which indicates a specific effect of CD40L. In addition, either depletion of mitochondria ( 0 cells, ie, mitochondria-depleted cells, to prevent mitochondrial O 2 ⅐ Ϫ ) or adenoviral overexpression of superoxide dismutase, as well as inhibition of NO synthase, abolished the CD40L-enhanced PGIS nitration, which implies that the mitochondria might be the source of O 2 ⅐ Ϫ and thus peroxynitrite (ONOO Ϫ ). Furthermore, SQ29548, a thromboxane A 2 /prostaglandin H 2 receptor antagonist, significantly reduced CD40L-enhanced expression of intercellular adhesion molecule-1. Finally, administration of CD40L resulted in PGIS inhibition and nitration in the aortas of C57BL6 mice but less in mice overexpressing human superoxide dismutase, which suggests that ONOO Ϫ might be required for CD40L-enhanced PGIS nitration in vivo. Conclusions-We

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“…Indeed, myeloperoxidase in the presence of nitrite and H 2 O 2 can cause nitration of proteins (Sampson et al, 1998). Based upon our current knowledge, it cannot be excluded that nitrite derived from increased iNOS activity could contribute to peroxynitrite-independent protein nitration in our model of cardiac allograft rejection.…”

mentioning

confidence: 78%

“…Traditionally, immunodetection of nitrotyrosine has been used as evidence of peroxynitrite formation in biological tissue. More recently, it has been shown that protein nitration may, under some conditions, arise independently of peroxynitrite via the action of MPO and nitrite (Eiserich et al, 1998;Sampson et al, 1998;Gaut et al, 2002). Although the precise pathways contributing to nitration in acute cardiac rejection have not yet been determined with certainty, a role of iNOS in nitrotyrosine formation has been indicated.…”

Section: Discussionmentioning

confidence: 99%

Protective Mechanisms of a Metalloporphyrinic Peroxynitrite Decomposition Catalyst, WW85, in Rat Cardiac Transplants

Pieper¹,

Nilakantan²,

Chen³

et al. 2005

J Pharmacol Exp Ther

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Nitric oxide (NO) derived from inducible NO synthase has been implicated in cardiac rejection. However, little is known about the role of the reactive nitrogen species peroxynitrite. We examined the protective actions of a peroxynitrite decomposition catalyst, WW85, in an experimental model of acute cardiac rejection. Heterotopic, abdominal transplantation of rat donor hearts was performed. Groups included isografts, allografts, or allografts treated with WW85, cyclosporine, or cyclosporine ϩ WW85. We determined graft survival, histological rejection, and graft function (by in situ sonomicrometry). Intragraft biochemical analysis of cytokines and proapoptotic and antiapoptotic gene expression using reverse transcriptase-polymerase chain reaction were determined. Treatment with WW85 or cyclosporine alone prolonged graft survival, improved graft function, and decreased histological rejection. Graft survival was further significantly (P Ͻ 0.001) enhanced by combination treatment. A decrease was also shown in nitrotyrosine, poly(ADP-ribose) polymerase (PARP) activation, and lipid peroxide formation by WW85 that was potentiated when given in combination with cyclosporine. Benefits could not be ascribed to changes in intragraft myeloperoxidase activity. Only combination therapy produced significant decreases in inflammatory cytokine gene expression, suggesting that WW85 acted primarily downstream of these stimuli. In general, WW85 had no direct action on expression of the proapoptotic gene, Fas ligand; however, WW85 given alone or with cyclosporine enhanced expression of antiapoptotic genes Bcl-2 and Bcl-xL. Collectively, these findings suggest a protective action of the peroxynitrite decomposition catalyst WW85 on graft rejection that is independent of any action on leukocyte sequestration and cytokine gene expression. Rather, effects seem to be downstream on decreased protein nitration, decreased lipid peroxidation, and decreased PARP activation.

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Myeloperoxidase and Horseradish Peroxidase Catalyze Tyrosine Nitration in Proteins from Nitrite and Hydrogen Peroxide

Cited by 306 publications

References 51 publications

Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia

Nitrated proteins in bronchoalveolar lavage fluid of patients at risk of ventilator-associated bronchopneumonia

CD40 Ligand–Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo

Protective Mechanisms of a Metalloporphyrinic Peroxynitrite Decomposition Catalyst, WW85, in Rat Cardiac Transplants

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