Journal article
Regulation of Renin Gene Expression by Oxidative Stress
Hypertension (Dallas, Tex. 1979), Vol.53(6), pp.1070-1076
06/2009
DOI: 10.1161/HYPERTENSIONAHA.109.130633
PMCID: PMC2740736
PMID: 19433777
Abstract
Increased arterial pressure, angiotensin II (Ang II) and cytokines each result in feedback inhibition of renin gene expression. Since Ang II and cytokines can stimulate reactive oxygen species (ROS) production, we tested the hypothesis that oxidative stress may be a mediator of this inhibition. Treatment of renin-expressing As4.1 cells with the potent cytokine TNFα caused an increase in the steady state levels of cellular ROS, which was reversed by the antioxidant N-acetylcysteine. Exogenous H
2
O
2
caused a dose- and time-dependent decrease in the level of endogenous renin mRNA, and decreased the transcriptional activity of a 4.1kb renin promoter fused to luciferase which was maximal when the renin enhancer was present. The effect of H
2
O
2
appeared to be specific to renin as there was no change in expression of β-actin or cyclophillin mRNA, nor transcriptional activity of the SV40 promoter. The TNFα-induced decrease in renin mRNA was partially reversed by either N-acetylcysteine or panepoxydone, an NFκB inhibitor. Interestingly, H
2
O
2
did not induce NFκB in As4.1 cells, and panepoxydone had no effect the down-regulation of renin mRNA by H
2
O
2
. The transcriptional activity of a cAMP response element (CRE)-luciferase construct was decreased by both TNFα and H
2
O
2
. These data suggest that cellular ROS can negatively regulate renin gene expression via an NFκB-independent mechanism involving the renin enhancer and inhibiting CRE-mediated transcription. Our data further suggest that TNFα decreases renin expression through both NFκB-dependent and NFκB-independent mechanisms, the latter involving the production of ROS.
Details
- Title: Subtitle
- Regulation of Renin Gene Expression by Oxidative Stress
- Creators
- Hana Itani - Molecular and Cellular Biology Graduate Program Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USAXuebo Liu - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USAEhab H Sarsour - Department of Radiation Oncology Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USAPrabhat C Goswami - Department of Radiation Oncology Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USAElla Born - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USAHenry L Keen - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USACurt D Sigmund - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.53(6), pp.1070-1076
- DOI
- 10.1161/HYPERTENSIONAHA.109.130633
- PMID
- 19433777
- PMCID
- PMC2740736
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 06/2009
- Academic Unit
- Molecular Physiology and Biophysics; Radiation Oncology; Neuroscience and Pharmacology; Iowa Institute of Human Genetics
- Record Identifier
- 9984046824402771
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