Coordinated upregulation of a series of endogenous antioxidants and phase 2 enzymes as a novel strategy for protecting renal tubular cells from oxidative and electrophilic stress

Experimental Biology and Medicine
Hong ZhuYunbo Li

Abstract

In view of the crucial involvement of oxidative and electrophilic stress in various kidney disorders, this study was undertaken to test the hypothesis that pharmacologically-mediated coordinated upregulation of endogenous renal antioxidants and phase 2 enzymes is an effective strategy for renal protection. Notably, studies on the pharmacological inducibility of a series of antioxidants and phase 2 enzymes in renal tubular cells are lacking. Here we reported that incubation of normal rat kidney (NRK-52E) proximal tubular cells with low micromolar concentrations (10-50 microM) of the cruciferous nutraceutical, 1,2-dithiole-3-thione (D3T), led to a significant concentration-dependent induction of a wide spectrum of antioxidants and phase 2 enzymes, including catalase (CAT), reduced form of glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1), and heme oxygenase (HO). We further observed that D3T treatment also increased the protein and mRNA expression for CAT, gamma-glutamylcysteine ligase, GR, GST-A, GST-M, NQO1, and HO-1. Incubation of the renal tubular cells with H(2)O(2), SIN-1-derived peroxynitrite, or 4-hydroxy-2-nonenal led to c...Continue Reading

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Citations

Jun 22, 2013·Experimental & Molecular Medicine·Elena Maria Yubero-SerranoJose Lopez-Miranda
Jul 2, 2011·The American Journal of Chinese Medicine·Chun-Ri LiYi-Guo Chen
Oct 29, 2013·Annual Review of Physiology·Meghan Delmastro-GreenwoodStacy Gelhaus Wendell

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Methods Mentioned

BETA
protein assay
PCR
electrophoresis

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