Evidence map›Paper›PMID 25627690›Full record

ArticleThe Journal of biological chemistry2015

Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)-homoserine lactone.

Christian Schwarzer, Zhu Fu, Takeshi Morita, Aaron G Whitt, Aaron M Neely, Chi Li, Terry E Machen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Trial
  2. Article
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  4. Review
  5. Article
  6. Heliyon · 2023
    Article
  7. Article
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  9. Article
  10. Article
  11. International journal of molecular sciences · 2021
    Article
  12. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Human Paraoxonase-2 (PON2): Protein Functions and Modulation.Antioxidants (Basel, Switzerland) · 2021
    Review
  14. Article
  15. 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

7 authors at 2 institutions in 1 country.

Christian SchwarzerFrom the Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 and.
Zhu FuFrom the Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 and.
Takeshi MoritaFrom the Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 and.
Aaron G Whittthe Departments of Medicine, Pharmacology, and Toxicology, Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202.
Aaron M Neelythe Departments of Medicine, Pharmacology, and Toxicology, Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202.
Chi Lithe Departments of Medicine, Pharmacology, and Toxicology, Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202.
Terry E MachenFrom the Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 and tmachen@berkeley.edu.
University of California, Berkeley · USUniversity of Louisville · US

Funding

NDC for the Optical Control of Biological FunctionPN2EY018241 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2006 to 2015
$37.5M
PROJ 12: STEM CELL-BASED VACCINE FOR CANCER PROPHYLAXISP20RR018733 · NCRR · UNIVERSITY OF LOUISVILLE · PI YADDANAPUDI, KAVITHA · 2003 to 2011
$18.9M
Activating Bax as a therapeutic strategy for lung cancerR01CA175003 · NCI · UNIVERSITY OF LOUISVILLE · PI LI, CHI · 2013 to 2017
$1.5M
Regulation of apoptosis by Bcl-XL, Bak and BaxK01CA106599 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LI, CHI · 2005 to 2009
$787k
MECHANISM OF H+ AND CL- TRANSPORT BY GASTRIC MUCOSAR01AM010141 · AM · UNIVERSITY OF CALIFORNIA BERKELEY · PI FORTE, JOHN G · 1985 to 1985
–
NCI NIH HHS K01 CA106599NCI NIH HHS K01CA106599NCI NIH HHS R01 CA175003NCRR NIH HHS P20 RR018733NCRR NIH HHS P20RR018733NEI NIH HHS PN2 EY018241NEI NIH HHS PN2-EY-018241NIADDK NIH HHS R01AM10141
6 · The paper itself

Abstract

Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (Δψmito) depolarized; Ca(2+) was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca(2+)] (Cacyto); and caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, quantitative PCR, and Western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), whereas DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: Δψmito depolarized, Cacyto increased, and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control Δψmito, Ca(2+) release from the ER, and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin and staurosporine, but activates Bax- and Bak-independent apoptosis in response to C12.

Indexed as

ApoptosisQuorum Sensing4-ButyrolactoneAnimalsAryldialkylphosphataseCells, CulturedHEK293 CellsHomoserineHost-Pathogen InteractionsHumansMicePseudomonas aeruginosaPseudomonas Infections4-ButyrolactoneAryldialkylphosphataseHomoserineN-(3-oxododecanoyl)homoserine lactonePON2 protein, humanPON2 protein, mouseApoptosisBaxCancerParaoxonase 2Pseudomonas aeruginosa (P. aeruginosa)Quorum Sensing

Identifiers

PMID25627690
PMCPMC4358143
OpenAlexW2320610764

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.