title: 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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shi
authors.forename: Yanping
authors.initials: Y
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Aiping
authors.initials: A
authors.lastname: Yin
authors.forename: Mei
authors.initials: M
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawai
authors.forename: Isamu
authors.initials: I
authors.lastname: Miyamori
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Fan
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D020868:Gene Silencing; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis*; D000074624:NADPH Oxidase 1; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D015854:Up-Regulation; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: C412373:AG 1879; D051697:Activating Transcription Factor 1; D000451:Mineralocorticoid Receptor Antagonists; D011743:Pyrimidines; D003609:Dactinomycin; D000450:Aldosterone; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat; D019061:src-Family Kinases