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Acta Physiologica 2007; Volume 191, Supplement 658
Joint Meeting of The Slovak Physiological Society, The Physiological Society and The Federation of European Physiological Societies
9/11/2007-9/14/2007
Bratislava, Slovakia
MECHANISMS OF ANGIOTENSIN IIMEDIATED INDUCTION OF THE EXPRESSION OF CYP11B2 IN HUMAN AND RAT ADRENOCORTICAL CELLS
Abstract number: OF23-89
Szekeres1 M., Cserzo1 M., Supeki1 K., Szidonya1 L., Turu1 G., Hazay1 M., Chaplin2 T., Clark2 A.J.L., Hunyady1 L.
1Dept. Physiol., Semmelweis Univ., Faculty of Medicine, Budapest, Hungary
2Dept. Endocrinol., Barts & The London, Queen Mary School of Medicine,London, United Kingdom; [email protected]
Aims:
Angiotensin II (AngII) activates several signaling pathways mediating physiological and pathophysiological responses in different cell types and organs, such as vasoconstriction, cell-proliferation, inflammation and atherosclerosis. It is known, that aldosterone synthase (CYP11B2) is regulated via calmodulin kinases (CAMK) and transcription factors (e.g. Nurr1/ NGFIB). Our purpose was to investigate AngII-induced transcriptional effects and signaling mechanisms in human and rat adrenocortical cells.
Methods:
Human adrenocortical cells (H295R) were subjected to microarray analysis. 2-hour AngII (1mM) stimulation upregulated more than 200 genes. Some genes of steroidogenesis and transcription factors were evaluated by real-time PCR. To investigate AngII-induced signalling mechanisms, we applied specific inhibitors: MEK inhibitor (PD98059, 20mM), PKC inhibitor (BIM1, 3mM), CAMK inhibitor (KN93, 10mM).
Results:
In H295R cells AngII induced expression of transcription factors Nurr1 (NR4A2) and NGFIB (NR4A1) by around 25- and 10-fold, respectively. CYP11B2, was induced by 5-fold. In rat glomerulosa cells, AngII induced 4-fold stimulation of the expression of CYP11B2, whereas transcription factor NGFIB was more activated than Nurr1 (11- over 2-fold). PD98059 and KN93 reduced AngII-induced activation of both Nurr1 and CYP11B2 in H295R cells such as NGFIB in rat cells. Activation of rat CYP11B2 was reduced by KN93.
Conclusion:
Angiotensin II-induced activation of CYP11B2 involves MAP-kinases and CAMK in humans and CAMK in rats. In rat glomerulosa cells NGFIB may have a dominant role over Nurr1. Supported by Grants OTKA T49851 and Jedlik Anyos 1/010/2005.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 191, Supplement 658 :OF23-89