Activation of Src-ATF1 pathway is involved in upregulation of Nox1, a catalytic subunit of NADPH oxidase, by aldosterone

Abstract

In this study, we mainly focused on how aldosterone regulates Nox1, a catalytic subunit of NADPH oxidase (NOX) in vascular smooth muscle cells (VSMC). We found that aldosterone can induce the expression of Nox1, which is upregulated by the activation of the Src and activating transcription factor 1 (ATF1), but can not be suppressed by the inhibitors of the epidermal growth factor receptor (EGFR) or Matrix Metalloproteinase (MMP). Aldosterone triggers ATF1 phosphorylation in dose dependent fashion, but this effect is not blocked by actinomycin D, suggesting a non-genomic effect of aldosterone. On the other hand, aldosterone induced Nox1 expression can be suppressed by the gene silencing of the ATF1 using RNA interference. Furthermore, silencing ATF1 can also attenuate aldosterone-induced O(2)(-) production and protein synthesis, and inhibit hypertrophy in this vascular cell lineage. In short, our results primarily unveiled the relationship between aldosterone and Nox1 expression and the regulation mechanism of their signal pathways in the hypertrophy of vascular smooth muscle cell. Src, ATF1, Nox1 and MR are likely efficient targets in the treating of vascular diseases but need more study.