Evidence map›Paper›PMID 27393890›Full record

ArticleRedox biology2016

Pleiotropic effects of 4-hydroxynonenal on oxidative burst and phagocytosis in neutrophils.

Balu K Chacko, Stephanie B Wall, Philip A Kramer, Saranya Ravi, Tanecia Mitchell, Michelle S Johnson, Landon Wilson, Stephen Barnes, Aimee Landar, Victor M Darley-Usmar

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

30 citing papers in PubMed, 50 citations in OpenAlex.

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  12. Immune interactions in pembrolizumab (PD-1 inhibitor) cancer therapy and cardiovascular complications.American journal of physiology. Heart and circulatory physiology · 2023
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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

10 authors at 3 institutions in 1 country.

Balu K ChackoMitochondrial Medicine Laboratory, University of Alabama at Birmingham, United States; Department of Pathology, University of Alabama at Birmingham, United States.
Stephanie B WallDepartment of Pathology, University of Alabama at Birmingham, United States.
Philip A KramerMitochondrial Medicine Laboratory, University of Alabama at Birmingham, United States; Department of Pathology, University of Alabama at Birmingham, United States.
Saranya RaviMitochondrial Medicine Laboratory, University of Alabama at Birmingham, United States; Department of Pathology, University of Alabama at Birmingham, United States.
Tanecia MitchellDepartment of Urology, University of Alabama at Birmingham, United States.
Michelle S JohnsonMitochondrial Medicine Laboratory, University of Alabama at Birmingham, United States; Department of Pathology, University of Alabama at Birmingham, United States.
Landon WilsonDepartment of Pharmacology and Toxicology, The Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, United States.
Stephen BarnesDepartment of Pharmacology and Toxicology, The Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, United States.
Aimee LandarDepartment of Pathology, University of Alabama at Birmingham, United States.
Victor M Darley-UsmarMitochondrial Medicine Laboratory, University of Alabama at Birmingham, United States; Department of Pathology, University of Alabama at Birmingham, United States. Electronic address: darley@uab.edu.
University of Alabama at Birmingham · USMitochondria Research and Medicine Society · USTarget (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume large quantities of oxygen to rapidly generate ROS, a process that is referred to as the oxidative burst. These ROS are required for the efficient removal of phagocytized cellular debris and pathogens. In chronic inflammatory diseases, neutrophils are exposed to increased levels of oxidants and pro-inflammatory cytokines that can further prime oxidative burst responses and generate lipid oxidation products such as 4-hydroxynonenal (4-HNE). In this study we hypothesized that since 4-HNE can target glycolysis then this could modify the oxidative burst. To address this the oxidative burst was determined in freshly isolated healthy subject neutrophils using 13-phorbol myristate acetate (PMA) and the extracellular flux analyzer. Neutrophils pretreated with 4-HNE exhibited a significant decrease in the oxidative burst response and phagocytosis. Mass spectrometric analysis of alkyne-HNE treated neutrophils followed by click chemistry detected modification of a number of cytoskeletal, metabolic, redox and signaling proteins that are critical for the NADPH oxidase mediated oxidative burst. These modifications were confirmed using a candidate immunoblot approach for critical proteins of the active NADPH oxidase enzyme complex (Nox2 gp91phox subunit and Rac1 of the NADPH oxidase) and glyceraldehyde phosphate dehydrogenase, a critical enzyme in the metabolic regulation of oxidative burst. Taken together, these data suggest that 4-HNE-induces a pleiotropic mechanism to inhibit neutrophil function. These mechanisms may contribute to the immune dysregulation associated with chronic pathological conditions where 4-HNE is generated.

Indexed as

AdultAldehydesCytoskeletal ProteinsGlycolysisHealthy VolunteersHumansLipid PeroxidationMiddle AgedNADPH OxidasesNeutrophilsPhagocytosisReactive Oxygen SpeciesRespiratory Burst4-hydroxy-2-nonenalAldehydesCytoskeletal ProteinsNADPH OxidasesReactive Oxygen SpeciesHydroxynonenalInflammationLipid peroxidationMetabolismNADPH OxidaseNeutrophilsOxidative burstOxidative stress

Identifiers

PMID27393890
PMCPMC4939321
OpenAlexW2470618402

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.