Source:http://linkedlifedata.com/resource/pubmed/id/19949978
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-1-21
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pubmed:abstractText |
Mechanisms underlying the tissue-specific impact of cardiotonic steroids (CTS) on cell survival and death remain poorly understood. This study examines the role of Na(+),K(+)-ATPase alpha subunits in death of Madin-Darby canine kidney (MDCK) cells evoked by 24-h exposure to ouabain. MDCK cells expressing a variant of the alpha1 isoform, CTS-sensitive alpha1S, were stably transfected with a cDNA encoding CTS-resistant alpha1R-Na(+),K(+)-ATPase, whose expression was confirmed by RT-PCR. In mock-transfected and alpha1R-cells, maximal inhibition of (86)Rb influx was observed at 10 and 1000 muM ouabain, respectively, thus confirming high abundance of alpha1R-Na(+),K(+)-ATPase in these cells. Six-hour treatment of alpha1R-cells with 1000 muM ouabain led to the same elevation of the [Na(+)](i)/[K(+)](i) ratio that was detected in mock-transfected cells treated with 3 muM ouabain. However, in contrast to the massive death of mock-transfected cells exposed to 3 muM ouabain, alpha1R-cells survived after 24-h incubation with 1000 muM ouabain. Inversion of the [Na(+)](i)/[K(+)](i) ratio evoked by Na(+),K(+)-ATPase inhibition in K(+)-free medium did not affect survival of alpha1R-cells but increased their sensitivity to ouabain. Our results show that the alpha1R subunit rescues MDCK cells from the cytotoxic action of CTS independently of inhibition of Na(+),K(+)-ATPase-mediated Na(+) and K(+) fluxes and inversion of the [Na(+)](i)/[K(+)](i) ratio.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cardiac Glycosides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ouabain,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1573-675X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
55-62
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pubmed:meshHeading |
pubmed-meshheading:19949978-Animals,
pubmed-meshheading:19949978-Cardiac Glycosides,
pubmed-meshheading:19949978-Cell Line,
pubmed-meshheading:19949978-Dogs,
pubmed-meshheading:19949978-Enzyme Inhibitors,
pubmed-meshheading:19949978-Epithelial Cells,
pubmed-meshheading:19949978-Kidney,
pubmed-meshheading:19949978-Ouabain,
pubmed-meshheading:19949978-Potassium,
pubmed-meshheading:19949978-Protein Binding,
pubmed-meshheading:19949978-Rats,
pubmed-meshheading:19949978-Sodium,
pubmed-meshheading:19949978-Sodium-Potassium-Exchanging ATPase
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pubmed:year |
2010
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pubmed:articleTitle |
Cardiotonic steroid-resistant alpha1-Na+,K+-ATPase rescues renal epithelial cells from the cytotoxic action of ouabain: evidence for a Nai+,Ki+ -independent mechanism.
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pubmed:affiliation |
Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Technopôle Angus, 2901 Rachel Est, Montreal, QC H1W 4A4, Canada. ol_akimova@hotmail.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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