Involvement of NF-κB in the induction of NAD(P)H: Quinone oxidoreductase (DT-diaphorase) by hypoxia, oltipraz and mitomycin C

doi:10.1016/0006-2952(94)00544-V

Biochemical Pharmacology

Volume 49, Issue 3, 31 January 1995, Pages 275-282

https://doi.org/10.1016/0006-2952(94)00544-V Get rights and content

Abstract

The activity of the two-electron bioreductive enzyme DT-diaphorase (DTD) is induced by heat shock, hypoxic stress, oltipraz, and mitomycin C (MMC). Transcriptional induction is associated with nuclear factor binding to elements mediating immediate early responses including AP-1, though the DTD mRNA peaks at 24 hr. Electrophoretic mobility shift assays revealed that nuclear protein extracts from hypoxia-, oltipraz-, and MMC-treated cells bound a specific oligonucleotide probe corresponding to the NF-κB transcriptional binding site in two human cancer cell lines, HT29 and HepG2. The binding activity for the NF-κB site was induced with a time-course similar to that of the induction of DTD, and was delayed in comparison to the induction of AP-1 binding proteins. The time-courses of the NF-κB binding response to MMC, oltipraz and hypoxic treatment were similar, and binding was most pronounced at 24 hr. All three stimuli were associated with the late appearance of a higher molecular weight complex in HT29 but not in HepG2 cells, suggestive of the participation of additional rel family proteins in DNA binding in this cell line. Competition experiments indicated that the bound protein complex was specific for the NF-κB binding site. An immunodepletion assay showed that in each case the bound complex consisted of a heterodimer of the NF-κB proteins p50 and p65. These data suggest that hypoxia, oltipraz and MMC may each induce the overexpression of DTD through a mechanism involving the NF-κB response element in the DTD 5′-flanking region, and support a role for this element in the control of detoxication responses to environmental changes.

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Rapid communicationInvolvement of NF-κB in the induction of NAD(P)H: Quinone oxidoreductase (DT-diaphorase) by hypoxia, oltipraz and mitomycin C

Abstract

The hypoxic tumor cell: A target for selective cancer chemotherapy

Biochem Pharmacol

Metabolism of mitomycin C by DT-diaphorase: Role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells

Cancer Res

NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: Characterization of a mutation which modulates DT-diaphorase activity and mitomycin C sensitivity

Cancer Res

DT-diaphorase and cancer chemotherapy

Biochem Pharmacol

Biochemical effects of dithiolthione

Food Chem Toxicol

Effect of oltipraz upon the survival and detoxication pathways of human colon adenocarcinoma cells

Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants

J Biol Chem

Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin

Biochemistry

Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Characterization of a DNA-protein interaction at the antioxidant responsive element and induction by 12-O-tetradecanoylphorbol 13-acetate

J Biol Chem

Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis

Regulation of human NAD(P)H:quinone oxidoreductase gene: Role of AP-1 binding site contained within human antioxidant response element

J Biol Chem

Fos and Jun: the AP-1 connection

Cell

The role of Jun, Fos and the AP-1 complex in cell proliferation and transformation

Biochim Biophys Acta

Effects of mitomycin C on the expression of DT-diaphorase in cytochrome P450 reductase in human colon adenocarcinoma cell lines

Effects of hypoxia upon detoxicating enzyme activity and expression in HT29 colon adenocarcinoma cells

Cancer Res

Activation of AP-1 and of a nuclear redox factor, Ref-1, in the response of HT29 colon cancer cells to hypoxia

Mol Cell Biol

Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a post-translational mechanism

Cell

The inducible transcription activator NF-κB: Regulation by distinct protein subunits

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IκB: A specific inhibitor of the NFκB transcription factor

Science

A 65-KD of active NF-κB is required for inhibition of NF-κB by Iκb

Genes Dev

Rapid communication
Involvement of NF-κB in the induction of NAD(P)H: Quinone oxidoreductase (DT-diaphorase) by hypoxia, oltipraz and mitomycin C

Human NAD(P)H:quinone oxidoreductase (NQO₁) gene structure and induction by dioxin