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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-11-15
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pubmed:abstractText |
Cyclosporin A employed in treatment of organ allograft rejection, is associated with hypertension possibly due to endothelin-1. We studied transcriptional regulation of endothelin-1 by cyclosporin A in human endothelial cells using cell transfection experiments and reporter gene assays. Human umbilical vein endothelial cells were established expressing a fusion gene of the coding sequence of the firefly luciferase gene, placed under the control of the rat endothelin-1 promoter. Luciferase assays demonstrate 2.8-fold stimulation of the reporter gene by cyclosporin A (P < 0.01), and Northern blot analysis shows induction of prepro endothelin-1 mRNA. Transcription is tightly repressed in the absence of the immunosuppressant, its regulation occurs Ca(2+)-dependent. Lack of extra- or intracellular Ca2+ prevents cyclosporin A-dependent endothelin-1 gene transcription and mRNA induction. These data demonstrate transcriptional regulation of endothelin-1 over a range of several orders of magnitude in human umbilical vein endothelial cells by cyclosporin A via Ca(2+)-dependent mechanisms. They support the critical role of endothelin- in cyclosporin A-associated hypertension.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0014-2999
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
379
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
97-106
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pubmed:dateRevised |
2006-5-1
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pubmed:meshHeading |
pubmed-meshheading:10499377-Animals,
pubmed-meshheading:10499377-Blotting, Northern,
pubmed-meshheading:10499377-Calcium,
pubmed-meshheading:10499377-Cells, Cultured,
pubmed-meshheading:10499377-Chelating Agents,
pubmed-meshheading:10499377-Cyclosporine,
pubmed-meshheading:10499377-Egtazic Acid,
pubmed-meshheading:10499377-Endothelin-1,
pubmed-meshheading:10499377-Endothelium,
pubmed-meshheading:10499377-Female,
pubmed-meshheading:10499377-Fluorometry,
pubmed-meshheading:10499377-Galactosidases,
pubmed-meshheading:10499377-Genes, Reporter,
pubmed-meshheading:10499377-Humans,
pubmed-meshheading:10499377-Immunosuppressive Agents,
pubmed-meshheading:10499377-Luciferases,
pubmed-meshheading:10499377-Plasmids,
pubmed-meshheading:10499377-Pregnancy,
pubmed-meshheading:10499377-RNA, Messenger,
pubmed-meshheading:10499377-Rats,
pubmed-meshheading:10499377-Transfection,
pubmed-meshheading:10499377-Umbilical Veins
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pubmed:year |
1999
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pubmed:articleTitle |
Cyclosporin A induces prepro endothelin-1 gene transcription in human endothelial cells.
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pubmed:affiliation |
Klinik IV für Innere Medizin, University of Cologne, Germany. tobias.marsen@uni-koeln.de
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pubmed:publicationType |
Journal Article
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