Cardiac BNP gene activation by angiotensin II in vivo.
The transcription factors involved in the activation of cardiac gene expression by angiotensin II (Ang II) in vivo are not well understood. Here we studied the contribution of transcriptional elements to the activation of the cardiac B-type natriuretic peptide (BNP) gene promoter by Ang II in conscious rats and in angiotensin II type 1 receptor (AT1R) transgenic mice. Rat BNP luciferase reporter gene constructs were injected into the left ventricular wall. The mean luciferase activity was 1.8-fold higher (P<0.05) in the ventricles of animals subjected to 2-week Ang II infusion as compared with vehicle infusion. Our results indicate that GATA binding sites at -90 and -81 in the rat BNP promoter are essential for the in vivo response to Ang II. The GATA factor binding to these sites is GATA-4. BNP mRNA levels and GATA-4 binding activity are also increased in the hypertrophied hearts of aged AT1R transgenic mice.
Majalahti
Theresa
T
Department of Physiology, Biocenter Oulu, University of Oulu, Oulu FIN-90014, Finland.
Suo-Palosaari
Maria
M
Sármán
Balázs
B
Hautala
Nina
N
Pikkarainen
Sampsa
S
Tokola
Heikki
H
Vuolteenaho
Olli
O
Wang
Jun
J
Paradis
Pierre
P
Nemer
Mona
M
Ruskoaho
Heikki
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C084364:Gata6 protein, rat; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D018808:Transcription Factor AP-1; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D004247:DNA