Evidence map›Paper›PMID 20739289›Full record

ArticleThe Journal of biological chemistry2010

Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia.

Christian Schwarzer, Steven Wong, James Shi, Elizabeth Matthes, Beate Illek, Juan P Ianowski, Ryan J Arant, Ehud Isacoff, Horia Vais, J Kevin Foskett and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Pharmacology of T2R Mediated Host-Microbe Interactions.Handbook of experimental pharmacology · 2022
    Article
  5. Impact ofFrontiers in immunology · 2020
    Review
  6. Calcium Regulation of Bacterial Virulence.Advances in experimental medicine and biology · 2020
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. "Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in T84 colonic cells.American journal of physiology. Gastrointestinal and liver physiology · 2015
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Termination and activation of store-operated cyclic AMP production.Journal of cellular and molecular medicine · 2012
    Article
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

13 authors at 5 institutions in 2 countries.

Christian SchwarzerDepartment of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
Steven Wong
James Shi
Elizabeth Matthes
Beate Illek
Juan P Ianowski
Ryan J Arant
Ehud Isacoff
Horia Vais
J Kevin Foskett
Isabella Maiellaro
Aldebaran M Hofer
Terry E Machen
University of California, Berkeley · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USUniversity of Saskatchewan · CAVA Boston Healthcare System · US

Funding

NDC for the Optical Control of Biological FunctionPN2EY018241 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2006 to 2015
$37.5M
MOLECULAR PHYSIOLOGY OF MAMMALIAN INSP3 RECEPTORSR01MH059937 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI FOSKETT, JAMES KEVIN · 2000 to 2014
$5.0M
Electrophysiology of nuclear membrane InsP3 receptorR37GM056328 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI FOSKETT, JAMES KEVIN · 2011 to 2020
$4.9M
ELECTROPHYSIOLOGY OF NUCLEAR MEMBRANE INSP3 RECEPTORR01GM056328 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI FOSKETT, JAMES KEVIN · 1999 to 2010
$4.2M
STRUCTURAL REARRANGEMENTS IN CHANNEL GATINGR01NS035549 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 1996 to 2013
$4.1M
Store-operated cAMP signaling in colon pathophysiologyR21DK088197 · NIDDK · HARVARD MEDICAL SCHOOL · PI HOFER, ALDEBARAN M · 2010 to 2011
$352k
NEI NIH HHS PN2 EY018241NIDDK NIH HHS R21 DK088197NIGMS NIH HHS GM056328NIGMS NIH HHS R01 GM056328NIGMS NIH HHS R37 GM056328NIMH NIH HHS MH059937NIMH NIH HHS R01 MH059937NINDS NIH HHS R01 NS035549
6 · The paper itself

Abstract

The ubiquitous bacterium Pseudomonas aeruginosa frequently causes hospital-acquired infections. P. aeruginosa also infects the lungs of cystic fibrosis (CF) patients and secretes N-(3-oxo-dodecanoyl)-S-homoserine lactone (3O-C12) to regulate bacterial gene expression critical for P. aeruginosa persistence. In addition to its effects as a quorum-sensing gene regulator in P. aeruginosa, 3O-C12 elicits cross-kingdom effects on host cell signaling leading to both pro- or anti-inflammatory effects. We find that in addition to these slow effects mediated through changes in gene expression, 3O-C12 also rapidly increases Cl(-) and fluid secretion in the cystic fibrosis transmembrane regulator (CFTR)-expressing airway epithelia. 3O-C12 does not stimulate Cl(-) secretion in CF cells, suggesting that lactone activates the CFTR. 3O-C12 also appears to directly activate the inositol trisphosphate receptor and release Ca(2+) from the endoplasmic reticulum (ER), lowering [Ca(2+)] in the ER and thereby activating the Ca(2+)-sensitive ER signaling protein STIM1. 3O-C12 increases cytosolic [Ca(2+)] and, strikingly, also cytosolic [cAMP], the known activator of CFTR. Activation of Cl(-) current by 3O-C12 was inhibited by a cAMP antagonist and increased by a phosphodiesterase inhibitor. Finally, a Ca(2+) buffer that lowers [Ca(2+)] in the ER similar to the effect of 3O-C12 also increased cAMP and I(Cl). The results suggest that 3O-C12 stimulates CFTR-dependent Cl(-) and fluid secretion in airway epithelial cells by activating the inositol trisphosphate receptor, thus lowering [Ca(2+)] in the ER and activating STIM1 and store-operated cAMP production. In CF airways, where CFTR is absent, the adaptive ability to rapidly flush the bacteria away is compromised because the lactone cannot affect Cl(-) and fluid secretion.

Indexed as

4-ButyrolactoneAnionsCalciumCalcium SignalingCell Line, TransformedChloridesCyclic AMPCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEndoplasmic ReticulumEnzyme InhibitorsGene Expression RegulationHumansInositol 1,4,5-Trisphosphate ReceptorsMembrane ProteinsNeoplasm Proteins4-ButyrolactoneAnionsCalciumCFTR protein, humanChloridesCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorEnzyme Inhibitorshomoserine lactoneInositol 1,4,5-Trisphosphate ReceptorsMembrane ProteinsNeoplasm ProteinsSTIM1 protein, humanStromal Interaction Molecule 1

Identifiers

PMID20739289
PMCPMC2966100
OpenAlexW1972252674

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.