Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: Protection against reactive oxygen and nitrogen species‐induced cell injury

Abstract

Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2

Potent induction of total cellular GSH and NQO1 as well as mitochondrial GSH by 3H-1,2-dithiole-3-thione in SH-SY5Y neuroblastoma cells and primary human neurons: Protection against neurocytotoxicity elicited by dopamine, 6-hydroxydopamine, 4-hydroxy-2-nonenal, or hydrogen peroxide

“…However, the same D3T treatment of SH-SY5Y cells under the present experimental conditions failed to significantly induce other endogenous antioxidants and phase 2 enzymes, including SOD, catalase, GR, GPx, and GST ( Table 1), indicating that in neuronal SH-SY5Y cells different antioxidants and phase 2 enzymes might be regulated via distinct signaling pathways. In this context, our previous studies have demonstrated that GSH and NQO1 are the two most inducible cellular defenses following treatment with various chemoprotectants and nutraceuticals, including D3T, resveratrol, and alpha-lipoic acid (Zhu et al, 2005;Cao et al, 2006;Jia et al, 2007).…”

“…The exact signaling mechanism by which D3T mediates elevation of GSH and NQO1 in SH-SY5Y cells remains to be defined. Recently, the nuclear factor E2-related factor (Nrf2) has been reported to be a critical transcriptional activator for a variety of antioxidative and phase 2 genes, especially GCL and NQO1 in various types of tissues and cells (Zhu et al, 2005;Kobayashi and Yamamoto, 2006;Zhu et al, 2006). Whether such an Nrf2-dependent mechanism is also involved in D3T-induced elevation of GSH and NQO1 in neuronal cells warrants further investigation.…”

“…Cellular SOD activity was measured according to the procedures described before (Zhu et al, 2005). In brief, the reaction mix contained in 50 mM potassium phosphate buffer, pH 7.8, 1.33 mM diethylenetriaminepentaacetic acid, 1.0 U/ml catalase, 70 μM nitroblue tetrazolium, 0.2 mM xanthine, 50 μM bathocuproinedisulfonic acid, and 0.13 mg/ml bovine serum albumin.…”

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

“…In circumstances of oxidative stress, Nrf2 is released from Keap1 either by through oxidative modification of Keap1 or after phosphorylation by redox sensitive protein kinases, translocates to the nucleus and in combination with other transcription factors activates gene transcription of genes containing an antioxidant response element (ARE) in their promoter regions resulting in a cytoprotective adaptive response (Kobayashi and Yamamoto, 2005). This adaptive response is characterized by upregulation of a battery of antioxidative enzymes and decreased sensitivity to oxidative damage and cytotoxicity (Zhu et al, 2005;Osburn et al, 2006). The pathway mediated by Nrf2-keap1 is central importance in regulating expression of detoxifying and antioxidant genes and protecting against carcinogenesis and xenobiotic toxicity (Dinokova-Kostova et al, 2005;Lee and Surh, 2005).…”

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a central role in the regulation of antioxidant and phase 2 detoxifying enzymes and related proteins [27,28]. In the cytoplasm, Keap1 (Kelchlike ECH-associated protein 1) binds to Nrf2 and facilitates its ubiquitination and thereby prevents its translocation to the nucleus.…”