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The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner
Cellular & Molecular Biology Letters volume 16, pages226–235(2011)
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.
activating transcription factor-1
Dulbecco’s modified Eagle’s medium
fetal bovine serum
Mn(III)tetrakis(4-benzoic acid)porphyrin chloride
NADPH oxidase 1
reactive oxygen species
vascular smooth muscle cell
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These authors contributed equally to this work
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Fu, Y., Shi, G., Wu, Y. et al. The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner. Cell Mol Biol Lett 16, 226–235 (2011). https://doi.org/10.2478/s11658-011-0002-3