Evidence map›Paper›PMID 21262967›Full record

ArticleThe Journal of biological chemistry2011

Peroxiredoxin 6 phosphorylation and subsequent phospholipase A2 activity are required for agonist-mediated activation of NADPH oxidase in mouse pulmonary microvascular endothelium and alveolar macrophages.

Shampa Chatterjee, Sheldon I Feinstein, Chandra Dodia, Elena Sorokina, Yu-Chin Lien, Su Nguyen, Kris Debolt, David Speicher, Aron B Fisher

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

93 citing papers in PubMed, 143 citations in OpenAlex.

  1. Review
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  5. Novel insights into the lipid signalling in human spermatozoa.Human reproduction (Oxford, England) · 2025
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  19. Article
  20. A Peptide Inhibitor of Peroxiredoxin 6 Phospholipase AAntioxidants (Basel, Switzerland) · 2021
    Article

33 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Shampa ChatterjeeInstitute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA.
Sheldon I Feinstein
Chandra Dodia
Elena Sorokina
Yu-Chin Lien
Su Nguyen
Kris Debolt
David Speicher
Aron B Fisher
University of Pennsylvania · USThe Wistar Institute · US

Funding

Role of Prdx6 in the activation of NADPH oxidaseR01HL105509 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI FISHER, ARON B. · 2011 to 2015
$2.6M
NHLBI NIH HHS HL105509NHLBI NIH HHS R01 HL105509
6 · The paper itself

Abstract

Peroxiredoxin 6 (Prdx6), a bifunctional enzyme with glutathione peroxidase and phospholipase A2 (PLA(2)) activities, participates in the activation of NADPH oxidase 2 (NOX2) in neutrophils, but the mechanism for this effect is not known. We now demonstrate that Prdx6 is required for agonist-induced NOX2 activation in pulmonary microvascular endothelial cells (PMVEC) and that the effect requires the PLA(2) activity of Prdx6. Generation of reactive oxygen species (ROS) in response to angiotensin II (Ang II) or phorbol 12-myristate 13-acetate was markedly reduced in perfused lungs and isolated PMVEC from Prdx6 null mice. Rac1 and p47(phox), cytosolic components of NOX2, translocated to the endothelial cell membrane after Ang II treatment in wild-type but not Prdx6 null PMVEC. MJ33, an inhibitor of Prdx6 PLA(2) activity, blocked agonist-induced PLA(2) activity and ROS generation in PMVEC by >80%, whereas inhibitors of other PLA(2)s were ineffective. Transfection of Prx6 null cells with wild-type and C47S mutant Prdx6, but not with mutants of the PLA(2) active site (S32A, H26A, and D140A), "rescued" Ang II-induced PLA(2) activity and ROS generation. Ang II treatment of wild-type cells resulted in phosphorylation of Prdx6 and its subsequent translocation from the cytosol to the cell membrane. Phosphorylation as well as PLA(2) activity and ROS generation were markedly reduced by the MAPK inhibitor, U0126. Thus, agonist-induced MAPK activation leads to Prdx6 phosphorylation and translocation to the cell membrane, where its PLA(2) activity facilitates assembly of the NOX2 complex and activation of the oxidase.

Indexed as

Amino Acid SubstitutionAngiotensin IIAnimalsButadienesCarcinogensCell MembraneCytosolEndotheliumEnzyme ActivationEnzyme InhibitorsLungMacrophages, AlveolarMembrane GlycoproteinsMiceMice, Mutant StrainsMitogen-Activated Protein Kinase KinasesAngiotensin IIButadienesCarcinogensCybb protein, mouseEnzyme InhibitorsMembrane GlycoproteinsMitogen-Activated Protein Kinase KinasesNADPH Oxidase 2NADPH OxidasesNeuropeptidesneutrophil cytosolic factor 1NitrilesPeroxiredoxin VIPhospholipases A2Prdx6 protein, mouserac1 GTP-Binding ProteinRac1 protein, mouserac GTP-Binding ProteinsReactive Oxygen SpeciesTetradecanoylphorbol AcetateU 0126

Identifiers

PMID21262967
PMCPMC3064221
OpenAlexW2014152577

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.