Evidence map›Paper›PMID 27094494›Full record

ArticleFree radical biology & medicine2016

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration.

Jaeyul Kwon, Aibing Wang, Devin J Burke, Howard E Boudreau, Kristen J Lekstrom, Agnieszka Korzeniowska, Ryuichi Sugamata, Yong-Soo Kim, Liang Yi, Ilker Ersoy and 5 more

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 52 citations in OpenAlex.

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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

15 authors at 6 institutions in 2 countries.

Jaeyul Kwon *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Aibing Wang *Diabetes Cluster, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
Devin J BurkeLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Howard E BoudreauLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Kristen J LekstromLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Agnieszka KorzeniowskaLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Ryuichi SugamataLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Yong-Soo KimLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Liang YiDiabetes Cluster, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
Ilker ErsoyDepartment of Pathology and Anatomical Sciences, University of Missouri, Sch. of Medicine, Columbia, MO, USA.
Stefan JaegerLister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Kannappan PalaniappanDepartment of Computer Sciences, University of Missouri-Columbia, MO, USA.
Daniel R AmbrusoDepartment of Pediatrics, University of Colorado Sch. of Medicine, Denver, CO, USA.
Sharon H JacksonDiabetes Cluster, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
Thomas L LetoLaboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USNational Institute on Minority Health and Health Disparities · USUniversity of Missouri · USNational Center for Biotechnology Information · USUniversity of Colorado Denver · US

Funding

NOX family NADPH oxidases: roles in innate immunity and inflammatory diseaseZIAAI000614 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LETO, THOMAS · 2009 to 2024
$16.2M
STRUCTURE AND FUNCTION OF PHAGOCYTE PROTEINSZ01AI000614 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LETO, THOMAS · 1991 to 2008
$3.3M
Intramural NIH HHS Z01 AI000614Intramural NIH HHS ZIA AI000614
6 · The paper itself

Abstract

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-derived superoxide production. Both peroxidase- and lipase-deficient mutant forms of Prdx6 (Prdx6 C47S and S32A, respectively) failed to bind to or stabilize Nox1 components or support Nox1-mediated superoxide generation. Furthermore, the transition-state substrate analogue inhibitor of Prdx6 phospholipase A2 activity (MJ-33) was shown to suppress Nox1 activity, suggesting Nox1 activity is regulated by the phospholipase activity of Prdx6. Finally, wild type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which this antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing.

Indexed as

Wound HealingAmino Acid SequenceCell MovementColonEpitheliumGlutathione PeroxidaseHCT116 CellsHumansNADPNADPH Oxidase 1Peroxiredoxin VIPhospholipases A2PhosphorylationProtein BindingReactive Oxygen SpeciesSuperoxidesGlutathione PeroxidaseNADPNADPH Oxidase 1NOX1 protein, humanPeroxiredoxin VIPhospholipases A2PRDX6 protein, humanReactive Oxygen SpeciesSuperoxidesCell migrationNADPH oxidaseNox1PeroxidasePeroxiredoxin 6Phospholipase A(2)Prdx 6

Identifiers

PMID27094494
PMCPMC4929831
OpenAlexW2340559944

What OpenQuestion holds

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Registered trials

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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.