Superoxide via Sp3 Transcription Factor Up-Regulates Renal AT1 Receptor Function and Contributes to Hypertension
type: CreativeWork
description: Hypertension is the most prevalent disease condition in the US affecting every 1 in 3 American adults. Renin angiotensin system (RAS) predominately regulates blood pressure and fluid homeostasis in the body. Angiotensin II type 1 (AT1) receptor is the key component of RAS that is implicated in hypertension. Oxidative stress is considered one of the main causes of hypertension. Studies including in our own lab showed that oxidative stress increases renal AT1 receptor function and contributes to hypertension. However, the exact mechanism of oxidative stress mediated increase in blood pressure is not completely known. Recent studies suggested that redox-sensitive transcription factors Sp3 and/or NF-κB regulate basal gene expression of AT1 receptor. Therefore, we designed studies to investigate the role of Sp3 and NF-κB in oxidative stress mediated hypertension or high blood pressure. We also designed studies to investigate the specificity of reactive oxygen species (superoxide vs. hydrogen peroxide) in regulating AT1 receptor function and high blood pressure. Results from cell culture studies (HK2 cells) demonstrated that SOD-inhibitor DETC but not hydrogen peroxide significantly increased fluorescence levels of superoxide probe dihydroethidium (DHE). Similarly, H2O2, but not DETC, treatment increased the fluorescence of the H2O2-sensitive probe dichloro-dihydro-fluorescein (DCFH). In addition, DETC, but not H2O2, increased the nuclear accumulation of Sp3 and NF-κB proteins. This effect was attenuated with tempol treatment. Furthermore, DETC increased AT1 receptor mRNA and protein expressions, which were attenuated with tempol treatment. However, H2O2 did not have any significant effect on AT1 mRNA expression. Results from transfection studies suggest that Sp3 plasmid increased while Sp3 siRNA decreased AT1 receptor protein expression. However, NF-κB plasmid failed to increase AT1 receptor protein expression. Immunofluorescence and biotinylation studies demonstrated th…
abstract: Hypertension is the most prevalent disease condition in the US affecting every 1 in 3 American adults. Renin angiotensin system (RAS) predominately regulates blood pressure and fluid homeostasis in the body. Angiotensin II type 1 (AT1) receptor is the key component of RAS that is implicated in hypertension. Oxidative stress is considered one of the main causes of hypertension. Studies including in our own lab showed that oxidative stress increases renal AT1 receptor function and contributes to hypertension. However, the exact mechanism of oxidative stress mediated increase in blood pressure is not completely known. Recent studies suggested that redox-sensitive transcription factors Sp3 and/or NF-κB regulate basal gene expression of AT1 receptor. Therefore, we designed studies to investigate the role of Sp3 and NF-κB in oxidative stress mediated hypertension or high blood pressure. We also designed studies to investigate the specificity of reactive oxygen species (superoxide vs. hydrogen peroxide) in regulating AT1 receptor function and high blood pressure. Results from cell culture studies (HK2 cells) demonstrated that SOD-inhibitor DETC but not hydrogen peroxide significantly increased fluorescence levels of superoxide probe dihydroethidium (DHE). Similarly, H2O2, but not DETC, treatment increased the fluorescence of the H2O2-sensitive probe dichloro-dihydro-fluorescein (DCFH). In addition, DETC, but not H2O2, increased the nuclear accumulation of Sp3 and NF-κB proteins. This effect was attenuated with tempol treatment. Furthermore, DETC increased AT1 receptor mRNA and protein expressions, which were attenuated with tempol treatment. However, H2O2 did not have any significant effect on AT1 mRNA expression. Results from transfection studies suggest that Sp3 plasmid increased while Sp3 siRNA decreased AT1 receptor protein expression. However, NF-κB plasmid failed to increase AT1 receptor protein expression. Immunofluorescence and biotinylation studies demonstrated th…
author: Saleem, Mohammad
language: eng
keywords: AT1 receptors, Sp3 and NF-KB transcription factors, Superoxides, Hydrogen peroxide, Oxidative stress, Hypertension, HK2 cells, RAS, Tempol, DHE and DCFHDA
date published: 2016-12
date modified: 2026-07-24T02:33:01Z
provider: University of Houston
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Houston

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10657/5427