Inhibition of ERK and p38 MAP Kinases Inhibits Binding of Nrf2 and Induction of GCS Genes

Zipper, Laurie M.; Mulcahy, Ríona

doi:10.1006/bbrc.2000.3830

Cited by 223 publications

(151 citation statements)

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“…It is then translocated to the nucleus to form heterodimers with other leucine zipper proteins such as c-Jun and small Mafs. These complexes transactivate gene expression by binding to EpRE [65][66][67]. Two mechanisms have been proposed for Nrf2-Keap1 dissociation, i.e., Nrf2 phosphorylation and Keap1 modification.…”

Section: Discussionmentioning

confidence: 99%

“…There are reports suggesting that the signaling transduction pathways involved in EpRE activation are also in a gene-, cell-, or stimulator-specific manner. An example of this is the signaling pathways involved in the EpRE-mediated NQO-1 and GCL induction in HepG2 cells; protein kinase C (PKC) and ERK/p38MAPK were involved, respectively in their EpRE activation [66,69]. As to the signaling pathways responsible for GGT induction by HNE, recent studies from our laboratory suggest that ERK1/2 and P38MAPK mediate the induction of GGT mRNA V-2 through regulation of the activation of Nrf2 [31,87].…”

Section: Discussionmentioning

confidence: 99%

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γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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Abstractγ-Glutamyl transpeptidase (GGT) plays key roles in glutathione homeostasis and metabolism of glutathione S-conjugates. Rat GGT is transcribed via five tandemly arranged promoters into seven transcripts. The transcription of mRNAV is controlled by promoter 5. Previously we found that GGT mRNAV-2 was responsible for the induction of GGT in rat alveolar epithelial cells by 4-hydroxynonenal (HNE). In the current study, the underlying mechanism was investigated. Reporter deletion and mutation analysis demonstrated that an electrophile-response element (EpRE) in the proximal region of GGT promoter 5 (GP5) was responsible for the basal-and HNE-induced promoter activity. Gel-shift assays showed an increased binding activity of GP5 EpRE after HNE exposure. The nuclear content of NF-E2-related factor 2 (Nrf2) was significantly increased by HNE. The recruitment of Nrf2 to GP5 EpRE after HNE treatment was demonstrated by supershift and chromatin immunoprecipitation assays. The tissue expression pattern of GGT mRNA V was previously unknown. Using polymerase chain reaction, we found that GGT mRNAV-2 was expressed in many tissues in rat. Taken together, GGT mRNAV-2 is widely expressed in rat tissues and its basal and HNE-induced expression is mediated through EpRE/Nrf2 signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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“…Indeed, the expression of some enzymes implicated in antioxidant defences such as the enzymes for glutathione synthesis [235] and heme oxygenase [37] exhibit ERK1/2 dependency in the regulation of their expression (Fig. 6).…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

“…Secondly, some flavonoids or their oxidation products (phenoxyl radical, quinones) may induce moderate levels of oxidative stress based on their pro-oxidant effects which can induce the upregulation of antioxidant defence enzymes similar to the priming effect of low doses of radiation of low concentrations of hydrogen peroxide. The expression of some enzymes implicated in antioxidant defences such as the enzymes for glutathione synthesis [235] and heme oxygenase [37] exhibit ERK1/2 dependency in the regulation of their expression. Furthermore, the transcription of Cu/ZnSOD is regulated by the transcription factor ELK-1 [35] and the promoter for MnSOD expression contain binding sites for Sp1, AP-1, and CREB [35,47], all of which have been linked to regulation by ERK1/2 [34,182].…”

Section: Flavonoids: Neuroprotective Agents In Vivo and In Vitro?mentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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“…The genes directly activated by Nrf2 typically contain an antioxidant response element (ARE), a cis-acting DNA regulatory element with a core sequence of 5 0 -TGA(C/T)nnnGC(A/ G)-3 0 [2][3][4]. Several phase II detoxification and antioxidant genes are known to be regulated by Nrf2, including NAD(P)H:quinone oxidoreductase, glutathione-S-transferase, c-glutamylcysteine synthase, heme oxygenase-1 (HO-1), glutathione peroxidase, and thioredoxin [1].…”

Section: Introductionmentioning

confidence: 99%

Activation of the Nrf2/antioxidant response pathway increases IL-8 expression

Zhang

Chen²,

Song

et al. 2005

Eur. J. Immunol.

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Inhibition of ERK and p38 MAP Kinases Inhibits Binding of Nrf2 and Induction of GCS Genes

Cited by 223 publications

References 31 publications

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Activation of the Nrf2/antioxidant response pathway increases IL-8 expression

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