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

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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.

Abbreviations

ALD:

aldosterone

ATF:

activating transcription factor-1

CRE:

cAMP-response element

CREB:

CRE-binding protein

DMEM:

Dulbecco’s modified Eagle’s medium

DPI:

diphenylene iodonium

FBS:

fetal bovine serum

MnTBAP:

Mn(III)tetrakis(4-benzoic acid)porphyrin chloride

MR:

mineralocorticoid receptor

MTT,3:

(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide

NOX1:

NADPH oxidase 1

ROS:

reactive oxygen species

VSMC:

vascular smooth muscle cell

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Correspondence to Chunyuan Fan.

Additional information

These authors contributed equally to this work

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Key words

  • Aldosterone
  • Mitochondria
  • ATF-1
  • NOX1
  • VSMC