Beta-adrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro.
We have previously reported that addition of 8-bromocyclic AMP enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is known to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adrenergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10(-9) to 10(-5) mol/L) alone had no stimulatory effect on the expression of pOCAT (ANG N-1498/+18). In the presence of dexamethasone (10(-6) mol/L), however, isoproterenol enhanced the stimulatory effect on the dexamethasone on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta 1- and beta 2-adrenergic receptor antagonist) and ICI 118,551 (beta 2-adrenergic receptor antagonist) but not by the presence of atenolol (beta 1-adrenergic receptor antagonist). Furthermore, the addition of Rp-cAMP (an inhibitor of protein kinase A I and II) blocked the enhancing effect of isoproterenol. These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta 2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid-induced expression of the angiotensinogen gene in the liver.
Ming
M
M
University of Montreal, Maisonneuve-Rosemont Hospital Research Center, Montreal, Canada.
Wu
J
J
Lachance
S
S
Delalandre
A
A
Carrière
S
S
Chan
J S
JS
D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
D011943:Receptors, Adrenergic, beta; D000808:Angiotensinogen; D000804:Angiotensin II; D003907:Dexamethasone; D011433:Propranolol; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol