title: The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner.
abstract: High aldosterone (Ald) levels can induce hypertrophy of vascular smooth muscle cells (VSMCs), which carries high risks of heart failure. A previous study showed that Ald induces hypertrophy of VSMCs by up-regulating NOX1, a catalytic subunit of NADPH oxidase that produces superoxides. However, the precise mechanism remains unknown. Diphenylene iodonium (DPI) is known as an inhibitor of complex I in the mitochondrial respiratory chain, and it was also found to almost completely suppress the induction of NOX1 mRNA and the phosphorylation of activating transcription factor (ATF-1) by PGF2α or PDGF in a rat VSMC cell line. In this study, we found that the Ald-induced phosphorylation of ATF-1 and NOX1 expression was significantly suppressed by DPI. Silencing of ATF-1 gene expression attenuated the induction of NOX1 mRNA expression, and over-expression of ATF-1 restored Ald-induced NOX1 expression. On the basis of this data, we show that the mitochondria mediate aldosterone-induced NOX1 gene expression in an ATF-1-dependent manner.
authors.affiliation: Department of Nephrology, West China Hospital of Sichuan University, Guoxue Lane 37, WuHou Zone, Chengdu, 610041, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Fu
authors.forename: Gang
authors.initials: G
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawai
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Linlin
authors.initials: L
authors.lastname: Yue
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Xia
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 / Q000235:genetics / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D008928:Mitochondria / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D009861:Onium Compounds / Q000494:pharmacology; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: D051697:Activating Transcription Factor 1; D009861:Onium Compounds; D013481:Superoxides; D000450:Aldosterone; C007517:diphenyleneiodonium; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat