Transcriptional regulation of renal dopamine D1 receptor function during oxidative stress

Hypertension
Anees A Banday, Mustafa F Lokhandwala

Abstract

There exists a strong link between oxidative stress, renal dopaminergic system, and hypertension. It is reported that reactive oxygen species attenuate renal proximal tubular dopamine receptor (D1R) function, which disrupts sodium regulation and leads to hypertension. However, the mechanisms for renal D1R dysfunction are not clear. We investigated the role of redox-sensitive transcription factors AP1 and SP3 in transcriptional suppression of D1R gene and subsequent D1R signaling. Human kidney proximal tubular cells were treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol. In human kidney cells, BSO caused oxidative stress and reduced D1R mRNA and membrane receptor expression. Incubation of human kidney cells with SKF38393, a D1R agonist, caused a concentration-dependent inhibition of Na/K-ATPase. However, SKF38393 failed to inhibit Na/K-ATPase in BSO-treated cells. BSO increased AP1 and SP3 nuclear expression. Transfection with AP1- or SP3-specific siRNA abolished BSO-induced D1R downregulation. Treatment of rats with BSO for 4 weeks increased oxidative stress and SP3-AP1 expression and reduced D1R numbers in renal proximal tubules. These rats exhibited high blood pressure, and SKF38...Continue Reading

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Jul 24, 2013·Hypertension·Anees Ahmad Banday, Mustafa F Lokhandwala
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Citations

Dec 28, 2019·Journal of the American Heart Association·Anees A Banday, Mustafa F Lokhandwala
May 1, 2020·Antioxidants & Redox Signaling·Jian YangChunyu Zeng
Feb 7, 2019·The Pharmacogenomics Journal·Santiago CuevasPedro A Jose
Nov 17, 2016·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·N M KouyoumdzianM I Rosón
Oct 20, 2020·Clinical and Experimental Hypertension : CHE·Zeba FarooquiAnees Ahmad Banday

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