Role of AP-1 Activation in Regulation of Angiotensinogen Gene Expression Induced by AngⅡ / 生物化学与生物物理进展

ABSTRACT

Angiotensin Ⅱ(AngⅡ)can induce the expression of its precursor,angiotensinogen,in vascular smooth muscle cells(VSMC),which is related with increased activating protein-1(AP-1)binding to its cis-element located in the angiotensinogen gene promoter.In the present study,cycloheximide(CHX)was used as an inhibitor to interrupt c-Jun,the role of AP-1 in AngⅡ-induced its precursor gene activation was investigated by DNA-protein interaction and immunoblotting.The results showed that the level of c-Jun,the component of transcription factor AP-1,was significantly increased in the nucleus of VSMC after AngⅡ treatment.The majority of c-Jun was found in the nucleus but hardly detected in the cytoplasm by immunocytochemistry staining.Immunoprecipitation assays confirmed that AngⅡ could induce serine phosphorylation of c-Jun.EMSA results indicated that the level of phosphorylated of c-Jun had a positive correlation with AP-1 binding activity to cis-acting element of angiotensinogen gene and transcription activation of angiotensinogen.CHX inhibited AngⅡ-induced binding activity of AP-1 by reducing the phosphorylation of c-Jun,though it did not affect the expression of c-Jun.These findings suggest that the AP-1 phosphorylation induced by AngⅡ is one of the important mechanisms whereby AngⅡ regulates its precursor gene expression in feedback manner.It is found that CHX is an inhibitor to phosphorylation of c-Jun.