Artikel
Pattern of angiotensin II-stimulated transcription factors is cell-type specific
Das Muster der Angiotensin II stimulierten Transkriptionsfaktoren ist Zelltyp spezifisch
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Veröffentlicht: | 10. August 2005 |
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Gliederung
Text
Angiotensin (Ang) II, the major biologically active peptide of the renin-angiotensin system (RAS), exerts numerous actions on the cardiovascular system via the Ang II AT1 receptor, such as vasoconstriction and electrolyte balance, by mediating cell-type-specific calcium release and activation of a variety of transcription factors. Therefore we investigated the capability of Ang II to stimulate the transcription factors nuclear factor-kappaB (NFKB), nuclear factor of activated T-cells (NFAT) and activator protein-1 (AP1) via AT1 activation in two different cell lines, to determine cell-type-specific differences in the intracellular signaling mediated by the AT1 receptor.
HEK293 and COS-1 cells, transfected with a plasmid containing the AT1 cDNA, driven by a CMV promoter, were used for dual luciferase assays. For measurements the cells were co-transfected with plasmids encoding for firefly-luciferase driven by an NFKB-, NFAT-, or AP1-induced promoter and a plasmid encoding renilla-luciferase, which was used as an internal control. Cells were stimulated with Ang II (10-6 M) and the luciferase activity was measured 8 hours after the stimulation.
In both cell lines, increasing concentrations of the AT1 receptor led to a dose-dependent increase in luciferase production, whereas in HEK293 cells the luciferase activity was increased 5.2 fold by NFKB (baseline: unstimulated, AT1-untransfected HEK293 cells), 9.1 fold by NFAT and 23.8 fold by AP1. In COS-1 cells the luciferase activity was increased 1.8 fold by NFKB (baseline: unstimulated, AT1-untransfected COS-1 cells), 3.7 fold by NFAT and 3.1 fold by AP1.
Our results demonstrate the pattern of angiotensin II stimulated transcription factors is cell-type specific. This finding could be of great clinical relevance, since pharmacological targeting the AT1 receptor downstream could lead to cell-type-specific beneficial treatment properties.