|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0001455,
umls-concept:C0010674,
umls-concept:C0014609,
umls-concept:C0033809,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0086418,
umls-concept:C0257136,
umls-concept:C0458827,
umls-concept:C0596019,
umls-concept:C1167322,
umls-concept:C1515877,
umls-concept:C1879547,
umls-concept:C2752508
|
|
pubmed:issue |
45
|
|
pubmed:dateCreated |
2010-11-1
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-Butyrolactone,
http://linkedlifedata.com/resource/pubmed/chemical/Anions,
http://linkedlifedata.com/resource/pubmed/chemical/CFTR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STIM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/homoserine lactone
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
1083-351X
|
|
pubmed:author |
pubmed-author:ArantRyan JRJ,
pubmed-author:FoskettJ KevinJK,
pubmed-author:HoferAldebaran MAM,
pubmed-author:IanowskiJuan PJP,
pubmed-author:IllekBeateB,
pubmed-author:IsacoffEhudE,
pubmed-author:MachenTerry ETE,
pubmed-author:MaiellaroIsabellaI,
pubmed-author:MatthesElizabethE,
pubmed-author:SchwarzerChristianC,
pubmed-author:ShiJamesJ,
pubmed-author:VaisHoriaH,
pubmed-author:WongStevenS
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
5
|
|
pubmed:volume |
285
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
34850-63
|
|
pubmed:dateRevised |
2011-11-7
|
|
pubmed:meshHeading |
pubmed-meshheading:20739289-4-Butyrolactone,
pubmed-meshheading:20739289-Anions,
pubmed-meshheading:20739289-Calcium,
pubmed-meshheading:20739289-Calcium Signaling,
pubmed-meshheading:20739289-Cell Line, Transformed,
pubmed-meshheading:20739289-Chlorides,
pubmed-meshheading:20739289-Cyclic AMP,
pubmed-meshheading:20739289-Cystic Fibrosis,
pubmed-meshheading:20739289-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:20739289-Endoplasmic Reticulum,
pubmed-meshheading:20739289-Enzyme Inhibitors,
pubmed-meshheading:20739289-Gene Expression Regulation,
pubmed-meshheading:20739289-Humans,
pubmed-meshheading:20739289-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:20739289-Membrane Proteins,
pubmed-meshheading:20739289-Neoplasm Proteins,
pubmed-meshheading:20739289-Pseudomonas Infections,
pubmed-meshheading:20739289-Pseudomonas aeruginosa,
pubmed-meshheading:20739289-Quorum Sensing,
pubmed-meshheading:20739289-Respiratory Mucosa
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia.
|
|
pubmed:affiliation |
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
