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.
Key words: Aldosterone, Mitochondria, ATF-1, NOX1, VSMC
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Abbreviations used
- 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
Footnotes
These authors contributed equally to this work
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