Effects of reactive oxygen and nitrogen species on cyclooxygenase-1 and -2 activities

Fujimoto, Yohko; Uno, Eriko; Sakuma, Satoru

doi:10.1016/j.plefa.2004.06.002

Cited by 40 publications

(30 citation statements)

References 26 publications

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“…The data presented demonstrate and confirm previous literature reports [9,43] that peroxynitrite in the low nanomolar range acts as a potent endogenous activator of PGHS-1, which triggers TxA 2 formation and aggregation in human platelets. Several reports indicate a direct impact of peroxynitrite on platelet function [29,33].…”

Section: Concept Of the "Peroxide Tone"supporting

confidence: 90%

“…1C) a reduction in PGHS-1 activity and platelet aggregation can be observed, suggesting that in addition to other proteins PGHS becomes nitrated and inactivated. This has been observed for isolated PGHS [9] as well as in platelets [26].…”

Section: Sin-1 Releasessupporting

confidence: 66%

“…The activation of prostaglandin endoperoxide H 2 synthase (PGHS; COX) was summarized by the term "peroxide tone" [8,39,40], which describes that for the initiation and maintenance of the PGHS catalytic cycle, a steady presence of peroxides or peroxynitrite [9] is required. This unique property of the PGHS isoenzymes originates from their radical-based catalytic mechanism.…”

Section: Concept Of the "Peroxide Tone"mentioning

confidence: 99%

“…We could successfully reproduce these effects as shown in figure 1C. Other groups used washed platelets and treated them with peroxynitrite, which at low concentrations caused an increase in aggregation and TxA 2 release, whereas high concentrations resulted in protein oxidation and nitration [9,26,30,44] that inhibited PGHS [9,26] and reduced aggregation [26]. Because…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…Peroxides or peroxynitrite [8,9] convert the resting PGHS-1 into its active form in which a ferric heme together with a neighboring tyrosine (Tyr)-residue are converted to a ferryl species and a Tyr-radical, respectively. The interaction of this Tyr-radical with the substrate arachidonic acid yields an arachidonyl radical, which is capable of interacting with molecular oxygen to form 15-hydroperoxy-prostaglandin-9,11,-endoperoxide (PGG 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets

Schildknecht

Loo

Weber³

et al. 2008

Free Radical Biology and Medicine

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Endogenous peroxynitrite modulates PGHS-1-dependent thromboxane A2 formation and aggregation in human platelets Abstract Aggregation of activated platelets is considerably mediated by the autocrine action of thromboxane A2 (TxA2) which is formed in a prostaglandin endoperoxide H2 synthase-1 (PGHS-1 or COX-1)-dependent manner. The activity of PGHS-1 can be stimulated by peroxides, an effect termed "peroxide tone", that renders PGHS-1 the key regulatory enzyme in the formation of TxA2. Activated platelets release nitric oxide (*NO) and superoxide (O*2) but their interactions with the prostanoid pathway have been controversially discussed in platelet physiology and pathophysiology. The current study demonstrates that endogenously formed peroxynitrite at nanomolar concentrations, originating from the interaction of *NO and *O2, potently activated PGHS-1, which parallels TxA2 formation and aggregation in human platelets. Inhibition of the endogenous formation of either *NO or O*2 resulted in a concentration-dependent decline of PGHS-1 activity, TxA2 release, and aggregation. The concept of peroxynitrite as modulator of TxA2 formation and aggregation explains the interaction of *NO and O*2 with the PGHS pathway and suggests a mechanism by which antioxidants can regulate PGHS-1-dependent platelet aggregation. This may provide a molecular explanation for the clinically observed hyperreactivity of platelets in high-risk patients and serve as a basis for novel therapeutic interventions. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ÔØ Å ÒÙ× Ö ÔØ A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Section: Concept Of the "Peroxide Tone"supporting

confidence: 90%

Section: Sin-1 Releasessupporting

confidence: 66%

Section: Concept Of the "Peroxide Tone"mentioning

confidence: 99%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets

Schildknecht

Loo

Weber³

et al. 2008

Free Radical Biology and Medicine

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Peroxynitrite—An ugly biofactor?

Ascenzi

Masi

Sciorati³

et al. 2010

BioFactors

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Cellular damage occurring under oxidative conditions has been ascribed mainly to the formation of peroxynitrite (ONOOH/ONOO(-)) that originates from the reaction of NO(*) with O(2) (*-). The detrimental effects of peroxynitrite are exacerbated by the reaction with CO(2) that leads to ONOOC(O)O(-), which further decays to the strong oxidant radicals NO(2) (*) and CO(3) (*-). The reaction with CO(2), however, may redirect peroxynitrite specificity. An excessive formation of peroxynitrite represents an important mechanism contributing to the DNA damage, the inactivation of metabolic enzymes, ionic pumps, and structural proteins, and the disruption of cell membranes. Because of its ability to oxidize biomolecules, peroxynitrite is implicated in an increasing list of diseases, including neurodegenerative and cardiovascular disorders, inflammation, pain, autoimmunity, cancer, and aging. However, peroxynitrite displays also protective activities: (i) at high concentrations, it shows anti-viral, anti-microbial, and anti-parasitic actions; and (ii) at low concentrations, it stimulates protective mechanisms in the cardiovascular, nervous, and respiratory systems. The detrimental effects of peroxynitrite and related reactive species are impaired by (pseudo-) enzymatic systems, mainly represented by heme-proteins (e.g., hemoglobin and myoglobin). Here, we report biochemical aspects of peroxynitrite actions being at the root of its biomedical effects.

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Neurovascular Coupling Mediated by Neuronal Derived-Nitric Oxide: Mechanisms in Health and Dysfunction with Impact on Aging and Alzheimer’s Disease

Lourenço

Ledo

Barbosa

et al. 2016

Biochemistry of Oxidative Stress

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Effects of reactive oxygen and nitrogen species on cyclooxygenase-1 and -2 activities

Cited by 40 publications

References 26 publications

Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets

Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets

Peroxynitrite—An ugly biofactor?

Neurovascular Coupling Mediated by Neuronal Derived-Nitric Oxide: Mechanisms in Health and Dysfunction with Impact on Aging and Alzheimer’s Disease

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