The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner

Cellular & Molecular Biology Letters

Chunyuan Fan²  Qinjie Xia⁴  Linlin Yue⁴  Gang Shi¹  Isamu Miyamori⁵  Yasuyuki Kawai⁵  Qing Tian⁴  Yanping Fu⁴  Yong Wu³ 

[1]State Key Laboratory of Biotherapy, SiChuan University, Chengdu, China$$

[2]Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China$$The Second People’s Hospital in Chengdu, Chengdu, China$$

[3]The Second Out-Patient Institutions of the Chengdu Military Region, Chengdu, China$$

[4]Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China$$

[5]Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan$$

关键词: Aldosterone;    Mitochondria;    ATF-1;    NOX1;    VSMC;   

DOI  :  10.2478/s11658-011-0002-3

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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.

【 授权许可】

Unknown