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Regulation of Renin Gene Expression by Oxidative Stress
Author(s) -
Itani Hana Ahmad,
Liu Xuebo,
Sarsour Ehab H.,
Goswami Prabhat C.,
Born Ella,
Keen Henry L.,
Sigmund Curt D.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb499
Subject(s) - renin–angiotensin system , oxidative stress , tumor necrosis factor alpha , angiotensin ii , enhancer , downregulation and upregulation , mediator , gene expression , transcription factor , endocrinology , chemistry , reactive oxygen species , luciferase , endogeny , medicine , cytokine , regulation of gene expression , biology , transfection , gene , biochemistry , blood pressure
Increased arterial pressure, angiotensin II(AII), and cytokines each result in feedback inhibition of renin gene expression. Because AII 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 tumor necrosis factor‐á (TNFá) caused an increase in the steady‐state levels of cellular ROS, which was reversed by the antioxidant NAC. Exogenous H2O2 (HP) caused a dose‐ and time‐dependent decrease in the level of endogenous renin mRNA and decreased the transcriptional activity of a 4.1‐kb renin promoter fused to luciferase, which was maximal when the renin enhancer was present. The TNFá–induced decrease in renin mRNA was partially reversed by either NAC or panepoxydone, a nuclear factor êB (NFêB) inhibitor. Interestingly, HP did not induce NFêB in As4.1 cells, and panepoxydone had no effect on the downregulation of renin mRNA by HP. The transcriptional activity of a cAMP response element‐luciferase construct was decreased by both TNFá and HP. These data suggest that cellular ROS can negatively regulate renin gene expression via an NFêB‐independent mechanism involving the renin enhancer and inhibiting cAMP response element–mediated transcription. TNFá decreases renin expression through both NFêB‐dependent and NFêB‐independent mechanisms.