Angiotensin‐II‐induced expression of proto‐oncogene (c‐fos, jun‐B and c‐jun) mRNA in bovine adrenocortical fasciculata cells (BAC) is mediated by AT‐1 receptors

FEBS Letters

Ouali, R.¹  Jaillard, C.¹  Viard, I.¹  Saez, J.M.¹ 

[1] INSERM U 307, Hôpital Debrousse, 29 Rue Soeur Bouvier, 69322 Lyon Cedex 05, France

关键词: Proto-oncogene;    c-fos;    c-jun;    jun-B;    Adrenal;    Angiotensin-II;   

DOI  :  10.1016/0014-5793(92)81180-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have shown previously that angiotensin-II (A-II) controls proto-oncogene (c-fos, jun-B and c-jun) mRNA accumulation in bovine adrenal fasciculata cells (BAC). Since BAC contain both subtypes (AT-1 and AT-2) of the A-II receptor, we have investigated which subtype was involved in the effect of A-II on proto-oncogene mRNA by using a selective antagonist for AT-1 (DUP 753) and for AT-2 (CGP 42112A). DUP 753, but not CGP 421 12A, inhibited the stimulatory effect of A-II on proto-oncogene mRNA, with ID_3ds of 4 × 10⁻⁷ M, 7 × 10⁻⁷ M and 2 × 10⁻⁶ M for c-fos, jun-B and c-jun, respectively. Neither of the two antagonists by themselves had a direct effect on proto-oncogene mRNA. As the A-II AT-1 receptors are coupled to the phospholipase C system in BAC, we have investigated whether the A-II effects on the proto-oncogenes were mediated by protein kinase C (PKC) or by Ca²⁺ calmodulin. First, activation of PKC by the phorbol ester, PMA, increased the level of the three proto-oncogene mRNAs, whereas calcium ionophore had no effect. Second, staurosporine, a specific inhibitor of PKC, reduced the stimulatory action of A-II on proto-oncogene mRNA by 80–90%, whereas trifluoroperazine, an inhibitor of calmodulin, had no significant effect. These results demonstrate that the effects of A-II on proto-oncogene mRNA are mediated by AT1 receptor subtypes, mainly through activation of the PKC pathway.

【 授权许可】

Unknown