Source:http://linkedlifedata.com/resource/pubmed/id/18664589
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2008-10-20
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| pubmed:abstractText |
We analyzed the mechanisms underlying the ion transport induced by tert-butyl hydroperoxide (t-BOOH), a membrane-permeant oxidant that has been widely used as a model of oxidative stress, in human airway epithelial cells (Calu-3). We found that t-BOOH induced a short-circuit current that was composed of two distinct components, a peaked component (PC) and a sustained component (SC). Both components were reduced by the presence of H-89 (N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline) [10 microM, a protein kinase A (PKA) inhibitor] and clofilium (100 microM, a cAMP-dependent K+ channel inhibitor) but not by charybdotoxin (50 nM, a human intermediate conductance Ca2+-activated K+ channel inhibitor), suggesting that both PC and SC were generated through a common PKA-dependent/Ca2+-independent pathway. Notwithstanding, analyses of the physiological properties revealed that PC and SC were attributable to different pathways. PC, but not SC, was correlated with apical membrane Cl- conductance and was inhibited by the cyclooxygenase (COX)-2 inhibitor NS-398 (N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide; 10 microM). In contrast, SC, but not PC, was composed of a component sensitive to bumetanide (50 microM), an inhibitor of the basolateral Na+-K+-2Cl- cotransporter (NKCC1), and was abolished by the cytoskeleton dysfunction induced by cytochalasin D (10 microM) and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane carboxamide (Y-27632; 20 microM). Collectively, t-BOOH induces PKA-related anion secretion through two independent pathways: rapid activation of apical anion efflux through a COX-2-dependent/cytoskeleton-independent pathway and relatively delayed activation of NKCC1 for basolateral anion uptake through a COX-2-independent/cytoskeleton-dependent pathway.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Bicarbonates,
http://linkedlifedata.com/resource/pubmed/chemical/CFTR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Chloride Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/clofilium,
http://linkedlifedata.com/resource/pubmed/chemical/sodium-potassium-chloride...,
http://linkedlifedata.com/resource/pubmed/chemical/tert-Butylhydroperoxide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1521-0103
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
327
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
453-64
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| pubmed:meshHeading |
pubmed-meshheading:18664589-Amides,
pubmed-meshheading:18664589-Bicarbonates,
pubmed-meshheading:18664589-Cells, Cultured,
pubmed-meshheading:18664589-Chlorides,
pubmed-meshheading:18664589-Cyclic AMP,
pubmed-meshheading:18664589-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:18664589-Cyclooxygenase Inhibitors,
pubmed-meshheading:18664589-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:18664589-Cytoskeleton,
pubmed-meshheading:18664589-Epithelial Cells,
pubmed-meshheading:18664589-Humans,
pubmed-meshheading:18664589-Lung,
pubmed-meshheading:18664589-Oxidative Stress,
pubmed-meshheading:18664589-Pyridines,
pubmed-meshheading:18664589-Quaternary Ammonium Compounds,
pubmed-meshheading:18664589-Sodium-Potassium-Chloride Symporters,
pubmed-meshheading:18664589-tert-Butylhydroperoxide
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| pubmed:year |
2008
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| pubmed:articleTitle |
Dual pathway activated by tert-butyl hydroperoxide in human airway anion secretion.
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| pubmed:affiliation |
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. itoyasu@med.nagoya-u.ac.jp.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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