gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Transcriptional regulation of AT2R and ATBP by estrogens

Transkriptionelle Regulation des AT2-Rezeptors und des ATBP durch Östrogene

Meeting Abstract

Suche in Medline nach

  • J. Reinemund - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)
  • M. Katerbaum - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)
  • T. Unger - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)
  • J. Isensee - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)
  • U. Steckelings - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)
  • H. Funke-Kaiser - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (CCR)/Campus Charité Mitte (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP159

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch159.shtml

Veröffentlicht: 8. August 2006

© 2006 Reinemund et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

Angiotensin II is known to contribute to myocardial hypertrophy (MH). The trophic effects of Ang II have been attributed to its AT1 receptor (AT1R), while the AT2 receptor (AT2R) in many aspects (inflammation, fibrosis) counteracts AT1R actions. Data about the role of AT2R in MH are controversial. Estrogens seem to modify the proportion of AT1R/ AT2R in favour of AT2R. Moreover, polymorphism studies have shown that AT2R has beneficial effects in myocardial hypertrophy in women. A recently isolated AT2 binding protein (ATBP= ATIP), which is expressed in several different isoforms, seems essential for AT2R coupled growth inhibition. We hypothesized that estrogens regulate AT2R and ATBP on the promoter level, and analyzed the corresponding molecular mechanisms. A detailed RT-PCR expression analysis indicated that several cellular systems are suitable to examine the estrogen effects on ATBP and RAS components, with trefoil factor 1 (TFF1) as positve control. Transcriptional start sites were determined using 5´-RACE yielding two sites concerning hATIP and one site - in appropiate distance to a TATA box - in the case of hAT2R. Promoter luciferase reporter assays using serial deletion mutants identified a positive regulatory element in intron 1 of hAT2R, and an intermediate promoter activity of hATIP1 in several different cell types. Preliminary data indicate that E2 can stimulate the AT2R promotor in PC12W cells, but is not able to induce ATIP1 mRNA in EA.hy926 cells. Finally, a chromatin-immunoprecipitation (ChIP) assay was established to examine the effects of estrogens on hAT2R and hATIP1 in the chromatin context. We conclude that intron 1 of hAT2R contains a direct or indirect estrogen responsive element not present in the hATIP1 promoter.