Isolation and characterization of zebrafish NFE2

Pratt, Stephen J.; Drejer, Anna H.; Foott, Helen; Barut, Bruce A.; Brownlie, Alison; Postlethwait, John H.; Y, Kato; Yamamoto, Masayuki; Zon, Leonard I.

doi:10.1152/physiolgenomics.00112.2001

Cited by 23 publications

(29 citation statements)

References 46 publications

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“…Single zebrafish homologs of NF-E2 and NRF2 have been described previously (10,38). In examining the zebrafish genome and predicted protein set, we identified two predicted zebrafish homologs of mammalian NRF1, a predicted NRF3 ortholog, and a second predicted NRF2 form.…”

Section: Identification Of Nf-e2-related Factors In Zebrafish-mentioning

confidence: 99%

Nrf2b, Novel Zebrafish Paralog of Oxidant-responsive Transcription Factor NF-E2-related Factor 2 (NRF2)

Timme‐Laragy

Karchner

Franks

et al. 2012

Journal of Biological Chemistry

144

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Background: NRF2 is a transcription factor that regulates the oxidative stress response. Results: Zebrafish have duplicate nrf2 genes, nrf2a and nrf2b, with distinct functions during embryonic development. Conclusion: nrf2a and nrf2b have undergone subfunction partitioning; Nrf2b is a negative regulator of embryonic gene expression. Significance: Duplicate zebrafish nrf2 genes provide opportunities for new insights into developmental roles of NRF2.

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Section: Identification Of Nf-e2-related Factors In Zebrafish-mentioning

confidence: 99%

Nrf2b, Novel Zebrafish Paralog of Oxidant-responsive Transcription Factor NF-E2-related Factor 2 (NRF2)

Timme‐Laragy

Karchner

Franks

et al. 2012

Journal of Biological Chemistry

144

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“…Several other family members, such as BTB-CNC, allogeneic Bach1 and Bach2 (Oyake et al 1996), Nrf3 (Kobayashi et al 1999), and p45-NFE2 (Pratt et al 2002) have since been identified. Nrf2 is a leucine zipper/CNC protein, a polypeptide with a molecular weight of 66 kDa, and it is widely expressed in organs with hyperoxia consumption, such as the muscle, heart, vasculature, liver, kidney, brain, lung, skin, and digestive tract.…”

Section: Introductionmentioning

confidence: 99%

The role of Nrf2 in oxidative stress-induced endothelial injuries

Chen¹,

Lu²,

Chen³

et al. 2015

Journal of Endocrinology

335

244

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Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Numerous antioxidant pathways are involved in cellular redox homeostasis, among which the nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is perhaps the most prominent. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Keap1 acts as an adapter for cullin 3/ring-box 1-mediated ubiquitination and degradation of Nrf2, which decreases the activity of Nrf2 under physiological conditions. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases. The aim of the present review is to briefly summarize the mechanisms that regulate the Nrf2/Keap1-ARE signaling pathway and the latest advances in understanding how Nrf2 protects against oxidative stress-induced endothelial injuries. Further studies regarding the precise mechanisms by which Nrf2-regulated endothelial protection occurs are necessary for determining whether Nrf2 can serve as a therapeutic target in the treatment of cardiovascular diseases.

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“…However, because MafK lacks a transactivation domain, it regulates transcription through interaction with the cap‘n’collar (CNC) bZIP proteins, including Nrf2 and Bach1 (Toki et al, 2005; Igarashi and Sun, 2006; Blank, 2008). The Nrf2-MafK heterodimer serves as an activator (Pratt et al, 2002; Kobayashi and Yamamoto, 2006), whereas the Bach1-MafK heterodimer functions as a repressor because Bach1 harbors a transcription-repressing BTB/POZ domain (Toki et al, 2005; Igarashi and Sun, 2006; Blank, 2008). Moreover, heme binds to Bach1 through its cysteine-proline (CP) dipeptide-containing heme regulatory motifs (HRMs) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish

Zhang

Huang

et al. 2014

Disease Models &Amp; Mechanisms

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Using a zebrafish model of hepatoerythropoietic porphyria (HEP), we identify a previously unknown mechanism underlying heme-mediated regulation of exocrine zymogens. Zebrafish bach1b, nrf2a and mafK are all expressed in the zebrafish exocrine pancreas. Overexpression of bach1b or knockdown of nrf2a result in the downregulation of the expression of the exocrine zymogens, whereas overexpression of nrf2a or knockdown of bach1b cause their upregulation. In vitro luciferase assays demonstrate that heme activates the zymogens in a dosage-dependent manner and that the zymogen promoter activities require the integral Maf recognition element (MARE) motif. The Bach1b-MafK heterodimer represses the zymogen promoters, whereas the Nrf2a-MafK heterodimer activates them. Furthermore, chromatin immunoprecipitation (ChIP) assays show that MafK binds to the MARE sites in the 5′ regulatory regions of the zymogens. Taken together, these data indicate that heme stimulates the exchange of Bach1b for Nrf2a at MafK-occupied MARE sites and that, particularly in heme-deficient porphyria, the repressive Bach1b-MafK heterodimer dominates, which can be exchanged for the activating Nrf2a-MafK heterodimer upon treatment with hemin. These results provide novel insights into the regulation of exocrine function, as well as the pathogenesis of porphyria, and should be useful for designing new therapies for both types of disease.

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Isolation and characterization of zebrafish NFE2

Cited by 23 publications

References 46 publications

Nrf2b, Novel Zebrafish Paralog of Oxidant-responsive Transcription Factor NF-E2-related Factor 2 (NRF2)

Nrf2b, Novel Zebrafish Paralog of Oxidant-responsive Transcription Factor NF-E2-related Factor 2 (NRF2)

The role of Nrf2 in oxidative stress-induced endothelial injuries

Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish

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