Evidence map›Paper›PMID 26385079›Full record

ArticleFree radical biology & medicine2015

Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes.

Meghan Delmastro-Greenwood, Kara S Hughan, Dario A Vitturi, Sonia R Salvatore, George Grimes, Gopal Potti, Sruti Shiva, Francisco J Schopfer, Mark T Gladwin, Bruce A Freeman and 1 more

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 95 citations in OpenAlex.

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  7. The chemical biology of dinitrogen trioxide.Redox biochemistry and chemistry · 2024
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  11. Antioxidant Therapy in Cancer: Rationale and Progress.Antioxidants (Basel, Switzerland) · 2022
    Review
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  15. Review
  16. Nitro Fatty Acids (NOMolecules (Basel, Switzerland) · 2021
    Review
  17. Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Meghan Delmastro-GreenwoodDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Kara S HughanPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA.
Dario A VitturiDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Sonia R SalvatoreDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
George GrimesPharmaceutical Development Section, Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Gopal PottiPharmaceutical Development Section, Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.
Sruti ShivaDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA.
Francisco J SchopferDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA.
Mark T GladwinPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA.
Bruce A FreemanDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA. Electronic address: freerad@pitt.edu.
Stacy Gelhaus WendellDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh PA, 15261, USA. Electronic address: gstacy@pitt.edu.
University of Pittsburgh · USNational Institutes of Health Clinical Center · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MORA, ANA LUCIA · 2011 to 2020
$26.1M
Molecular Basis of Pediatric DiseaseK12HD052892 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TERENCE S. DERMODY · 2007 to 2026
$6.5M
Redox-Derived Pulmonary Anti-Inflammatory MediatorsR01HL064937 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2000 to 2015
$5.6M
Redox Transduction of Nitric Oxide SignalingR37HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2008 to 2017
$5.2M
Translational Pulmonary Vascular BiologyT32HL110849 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sruti Shiva · 2012 to 2026
$5.0M
NITRIC OXIDE REGULATION OF VASCULAR OXIDANT INJURYR01HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 1998 to 2007
$3.3M
Anti-Inflammatory Lipid Mediators in AsthmaR01HL132550 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN, HOLGUIN, FERNANDO · 2016 to 2019
$2.9M
Interdisciplinary CAM Curriculum ModelR25AT000682 · NCCIH · UNIVERSITY OF KENTUCKY · PI ELDER, WILLIAM GIBBS · 2002 to 2006
$1.6M
Nitrite Modulation of Hypertension, Platelet Activation and Endothelial and Mitochondrial FunctionK23HL124051 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUGHAN, KARA S. · 2015 to 2017
$471k
NCATS NIH HHS UL1 TR000005NCCIH NIH HHS AT00682NCCIH NIH HHS R25 AT000682NHLBI NIH HHS K23 HL124051NHLBI NIH HHS P01 HL103455NHLBI NIH HHS P01-HL103455NHLBI NIH HHS R01 HL058115NHLBI NIH HHS R01-HL058115NHLBI NIH HHS R01 HL064937NHLBI NIH HHS R01 HL132550NHLBI NIH HHS R01-HL64937NHLBI NIH HHS R37 HL058115NHLBI NIH HHS T32 HL110849NICHD NIH HHS K12 HD052892NICHD NIH HHS K12-HD052892
6 · The paper itself

Abstract

A gap in our understanding of the beneficial systemic responses to dietary constituents nitrate (NO3(-)), nitrite (NO2(-)) and conjugated linoleic acid (cLA) is the identification of the downstream metabolites that mediate their actions. To examine these reactions in a clinical context, investigational drug preparations of (15)N-labeled NO3(-) and NO2(-) were orally administered to healthy humans with and without cLA. Mass spectrometry analysis of plasma and urine indicated that the nitrating species nitrogen dioxide was formed and reacted with the olefinic carbons of unsaturated fatty acids to yield the electrophilic fatty acid, nitro-cLA (NO2-cLA). These species mediate the post-translational modification (PTM) of proteins via reversible Michael addition with nucleophilic amino acids. The PTM of critical target proteins by electrophilic lipids has been described as a sensing mechanism that regulates adaptive cellular responses, but little is known about the endogenous generation of fatty acid nitroalkenes and their metabolites. We report that healthy humans consuming (15)N-labeled NO3(-) or NO2(-), with and without cLA supplementation, produce (15)NO2-cLA and corresponding metabolites that are detected in plasma and urine. These data support that the dietary constituents NO3(-), NO2(-) and cLA promote the further generation of secondary electrophilic lipid products that are absorbed into the circulation at concentrations sufficient to exert systemic effects before being catabolized or excreted.

Indexed as

AdultAlkenesAnti-Inflammatory AgentsChromatography, LiquidDietary SupplementsFemaleHumansLinoleic AcidMaleNitratesNitritesNitro CompoundsSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationAlkenesAnti-Inflammatory AgentsLinoleic AcidNitratesNitritesNitro CompoundsConjugated linoleic acidDietNitrateNitriteNitro-fatty acidNitrogen metabolismRedox signaling

Identifiers

PMID26385079
PMCPMC4684780
OpenAlexW1743854985

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.