Evidence map›Paper›PMID 37460614›Full record

ArticleNature communications2023

The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils.

Juliana Escher Toller-Kawahisa, Carlos Hiroji Hiroki, Camila Meirelles de Souza Silva, Daniele Carvalho Nascimento, Gabriel Azevedo Públio, Timna Varela Martins, Luis Eduardo Alves Damasceno, Flávio Protásio Veras, Paula Ramos Viacava, Fábio Yuji Sukesada and 9 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

51 citing papers in PubMed, 61 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

19 authors at 3 institutions in 2 countries.

Juliana Escher Toller-KawahisaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. jutoller@hotmail.com.ORCID 0000-0001-7323-5036
Carlos Hiroji HirokiDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Camila Meirelles de Souza SilvaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.ORCID 0000-0001-8185-4435
Daniele Carvalho NascimentoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.ORCID 0000-0002-0620-339X
Gabriel Azevedo PúblioDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.ORCID 0000-0002-5643-409X
Timna Varela MartinsDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Luis Eduardo Alves DamascenoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.ORCID 0000-0003-2833-9244
Flávio Protásio VerasDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Paula Ramos ViacavaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Fábio Yuji SukesadaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Emily Anne DaySchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0003-3245-5715
Alessia ZottaSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.
Tristram Alexander Jasper RyanSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0003-0278-1878
Rodrigo Moreira da SilvaNPPNS, Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.
Thiago Mattar CunhaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Norberto Peporine LopesNPPNS, Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Ribeirao Preto, Brazil.ORCID 0000-0002-8159-3658
Fernando de Queiroz CunhaDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Luke Anthony John O'NeillSchool of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0002-4333-2748
José Carlos Alves-FilhoDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. jcafilho@usp.br.ORCID 0000-0002-9918-8714
Universidade de São Paulo · BRTrinity College Dublin · IEUniversidade de Ribeirão Preto · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophils rely predominantly on glycolytic metabolism for their biological functions, including reactive oxygen species (ROS) production. Although pyruvate kinase M2 (PKM2) is a glycolytic enzyme known to be involved in metabolic reprogramming and gene transcription in many immune cell types, its role in neutrophils remains poorly understood. Here, we report that PKM2 regulates ROS production and microbial killing by neutrophils. Zymosan-activated neutrophils showed increased cytoplasmic expression of PKM2. Pharmacological inhibition or genetic deficiency of PKM2 in neutrophils reduced ROS production and Staphylococcus aureus killing in vitro. In addition, this also resulted in phosphoenolpyruvate (PEP) accumulation and decreased dihydroxyacetone phosphate (DHAP) production, which is required for de novo synthesis of diacylglycerol (DAG) from glycolysis. In vivo, PKM2 deficiency in myeloid cells impaired the control of infection with Staphylococcus aureus. Our results fill the gap in the current knowledge of the importance of lower glycolysis for ROS production in neutrophils, highlighting the role of PKM2 in regulating the DHAP and DAG synthesis to promote ROS production in neutrophils.

Indexed as

NeutrophilsPyruvate KinaseGlycolysisPhosphorylationReactive Oxygen SpeciesPyruvate KinaseReactive Oxygen Species

Identifiers

PMID37460614
PMCPMC10352279
OpenAlexW4384499036

What OpenQuestion holds

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LicenceCC BY
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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.