Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH

Shi, Xianglin; Mao, Yan; Daniel, Lambert N.; Ahmed, Nadera; Saffiotti, Umberto; Rojanasakul, Yon; Gannett, Peter M.; Liu, Kejian

doi:10.1016/0162-0134(94)85039-9

Cited by 34 publications

(14 citation statements)

References 37 publications

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“…Other thiolic targets are the sulfhydryl groups in proteins and thiol-containing cofactors (i.e. coenzyme A, lipoic acid, thioredoxin, and phosphopantetheine), thus perturbing the integrated metabolic pathways and membrane-linked functions that participate in essential metabolic and biosynthetic processes [47,66].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Metabolite I of Erdosteine on the Generation of Nitric Oxide and Peroxynitrite Chemiluminescence by Human Neutrophils

Sasso

Culici²,

Bianchi³

et al. 2004

Pharmacology

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Polymorphonuclear neutrophils (PMNs) can generate superoxide anions and nitric oxide (NO), which is not only an important mediator of various cellular activities, but can also react with superoxide anions to produce peroxynitrite anions (ONOO^–). Peroxynitrite is a potent and potentially toxic oxidant that damages various types of biomolecules. It preferentially mediates the oxidation of thiolic groups in protein and non-protein molecules, thus altering their functions. The aim of this study was to examine whether, in addition to its ability to reduce the respiratory bursts of human PMNs, the SH metabolite I (Met I) of erdosteine, can interfere with NO and NO-derived peroxynitrite production, thus extending its antioxidant activity. This was done by means of the luminol amplified chemiluminescence (LACL), which has been widely used to detect the production of reactive oxidant species (ROS) by PMNs under various conditions. At 5 and 10 µg/ml, Met I significantly reduced LACL after fMLP and PMA stimulation. When L-Arg was added to the reaction medium, as a NO donor, the chemiluminescence of fMLP increased by up to 67% and that of PMA by up to 132%, but was once again significantly reduced by 5 and 10 µg/ml of Met I. In a cell-free system, the use of linsidomine (SIN-1) makes it possible to investigate the behavior of LACL induced by peroxynitrite release, which was significantly reduced by Met I concentrations ranging from 1.25 to 10 µg/ml. Our findings indicate that Met I, a molecule with a SH group, reacts with ROS, NO and NO-derived peroxynitrite, and has both antioxidant and scavenging activity. This is of interest for the strategy of protecting against damage induced by radical species in the pulmonary cell environment, in which they can induce a phlogogenic loop, and suggests that adding exogenous thiols may be useful in antagonizing the toxic effects of reactive molecules on endogenous thiols.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Metabolite I of Erdosteine on the Generation of Nitric Oxide and Peroxynitrite Chemiluminescence by Human Neutrophils

Sasso

Culici²,

Bianchi³

et al. 2004

Pharmacology

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“…It should be mentioned, however, that ascorbate y Ž and dithiothreitol can react with ONOO as well Radi et . al., 1991;Shi et al, 1994 , and were protective. Ascorbate and dithiothreitol, but not urate, increased the rate of decomposition of S-nitroso-N-acetylpenicillamine.…”

Section: Onoo Y May Not Be Inõolõed In Apoptosis Induced By S-nitrosomentioning

confidence: 99%

S-nitroso-N-acetylpenicillamine and nitroprusside induce apoptosis in a neuronal cell line by the production of different reactive molecules

Terwel¹,

Nieland²,

Schütte³

et al. 2000

European Journal of Pharmacology

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“…Experiments in our laboratory (5,6), conducted by single intratracheal instillation of quartz (min-U-sil 5 or HF-etched min-U-sil 5) in Fischer 344 rats, examined the development of the pathologic reactions to quartz observed at serial sacrifices from the first day to 6 months, then at 11 and 17 months, and then in rats that died afterwards (17)(18)(19)(20)(21)(22)(23)(24)(25)(26) months). The early phases of the lung reaction to quartz included recruitment of both alveolar and interstitial macrophages with uptake and internalization of particles.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.

Saffiotti

Daniel

Mao

et al. 1994

Environ Health Perspect

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MarylandThe carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type 11 cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type 11 hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type 11 cells. Immunohistochemical localization of TGF-,B1 precursor in alveolar type 11 cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides. -Environ Health Perspect 102(Suppl 10): 159-164(1994)

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Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH

Cited by 34 publications

References 37 publications

Inhibitory Effects of Metabolite I of Erdosteine on the Generation of Nitric Oxide and Peroxynitrite Chemiluminescence by Human Neutrophils

Inhibitory Effects of Metabolite I of Erdosteine on the Generation of Nitric Oxide and Peroxynitrite Chemiluminescence by Human Neutrophils

S-nitroso-N-acetylpenicillamine and nitroprusside induce apoptosis in a neuronal cell line by the production of different reactive molecules

Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.

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