Peroxiredoxin-4 and dopamine D5 receptor interact to reduce oxidative stress and inflammation in the kidney

Bibhas Amatya, The George Washington University School of Medicine and Health Sciences, 43989, Medicine, Washington, District of Columbia, United States; bibhasamatya78@gwmail.gwu.edu.
Sufei Yang, University of Maryland School of Medicine, 12264, Medicine, Baltimore, Maryland, United States; sufeiyang2014@163.com.
Peiying Yu, University of Maryland School of Medicine, 12264, Medicine, Baltimore, Maryland, United States; peiyingyu@ymail.com.
Pedro A S Vaz de Castro, The George Washington University School of Medicine and Health Sciences, 43989, Medicine, Washington, District of Columbia, United States; pedroasvc@gmail.com.
Ines Armando, The George Washington University School of Medicine and Health Sciences, 43989, Washington, District of Columbia, United States; iarmando@email.gwu.edu.
Chunyu Zeng, Daping Hospital, The Third Military Medical University, Chongqing, China; chunyuzeng01@163.com.
Robin A. Felder, University of Virginia School of Medicine, 12349, Charlottesville, Virginia, United States; raf7k@virginia.edu.
Laureano D. Asico, The George Washington University School of Medicine and Health Sciences, 43989, Medicine, Washington, District of Columbia, United States; lasico@email.gwu.edu.
Pedro A. Jose, The George Washington University School of Medicine and Health Sciences, 43989, Medicine, Washington, District of Columbia, United States; pjose@mfa.gwu.edu.
Hewang Lee, The George Washington University School of Medicine and Health Sciences, 43989, Department of Medicine, 2300 I Street, N.W., Walter G. Ross Hall, Suite 740, Washington, Washington, District of Columbia, United States, 20037; LIH@GWU.EDU.

Document Type

Journal Article

Publication Date

11-18-2022

Journal

Antioxidants & redox signaling

DOI

10.1089/ars.2022.0034

Abstract

AIMS: Reactive oxygen species are highly reactive molecules generated in different subcellular compartments. Both the dopamine D5 receptor (D5R) and endoplasmic reticulum-resident peroxiredoxin-4 (PRDX4) play protective roles against oxidative stress. This study is aimed at investigating the interaction between PRDX4 and D5R in regulating oxidative stress in the kidney. RESULTS: Fenoldopam (FEN), a D1R and D5R agonist, increased PRDX4 protein expression, mainly in non-lipid rafts, in D5R-HEK 293 cells. FEN increased the co-immunoprecipitation of D5R and PRDX4 and their colocalization, particularly in the endoplasmic reticulum. The efficiency of Förster resonance energy transfer was increased with FEN treatment measured with fluorescence lifetime imaging microscopy. Silencing of PRDX4 increased hydrogen peroxide production, impaired the inhibitory effect of FEN on hydrogen peroxide production, and increased the production of interleukin-1, tumor necrosis factor, and caspase-12 in renal cells. Furthermore, in Drd5-/- mice, which are in a state of oxidative stress, renal cortical PRDX4 was decreased whereas interleukin-1 , tumor necrosis factor, and caspase-12 were increased, relative to their normotensive wild-type Drd5+/+ littermates. INNOVATION: Our findings demonstrate a novel relationship between D5R and PRDX4 and the consequent effects of this relationship in attenuating hydrogen peroxide production in the endoplasmic reticulum and the production of proinflammatory cytokines. This study provides the potential for the development of biomarkers and new therapeutics for renal inflammatory disorders, including hypertension. CONCLUSION: PRDX4 interacts with D5R to decrease oxidative stress and inflammation in renal cells which may have potential of translational significance.

Department

Medicine

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