Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TCDD (2,3,7,8-tetrachlorodibenzo- p -dixoin) induces phase II drug-metabolizing enzyme NQO1 [NAD(P)H:quinone oxidoreductase; EC 1.6.99.2; DT-diaphorase] in a wide range of mammalian tissues and cells. Here, we analysed the molecular pathway mediating NQO1 induction by TCDD in mouse hepatoma cells. Inhibition of protein synthesis with CHX (cycloheximide) completely blocks induction of NQO1 by TCDD as well as the basal expression and induction by phenolic antioxidant tBHQ (2-t-butylbenzene-1,4-diol), implicating a labile factor in NQO1 mRNA expression. The inhibition is both time- and concentration-dependent, requires inhibition of protein synthesis, and occurs at a transcriptional level. Inhibition of NQO1 transcription by CHX correlates with a rapid reduction of the CNC bZip (cap 'n' collar basic leucine zipper) transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) through the 26 S proteasome pathway. Moreover, blocking Nrf2 degradation with proteasome inhibitor MG132 increases the amount of Nrf2 and superinduces NQO1 in the presence of TCDD or tBHQ. Finally, genetic experiments using AhR (aryl hydrocarbon receptor)-, Arnt (aryl hydrocarbon receptor nuclear translocator)- or Nrf2-deficient cells reveal that, while induction of NQO1 by TCDD depends on the presence of AhR and Arnt, the basal and inducible expression of NQO1 by either TCDD or tBHQ requires functional Nrf2. The findings demonstrate a novel role of Nrf2 in the induction of NQO1 by TCDD and provide new insights into the mechanism by which Nrf2 regulates the induction of phase II enzymes by both phenolic antioxidants and AhR ligands.
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PMID:Induction of murine NAD(P)H:quinone oxidoreductase by 2,3,7,8-tetrachlorodibenzo-p-dioxin requires the CNC (cap 'n' collar) basic leucine zipper transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2): cross-interaction between AhR (aryl hydrocarbon receptor) and Nrf2 signal transduction. 1451 Jun 36

Monofunctional inducers (MIs) enhance phase 2 enzymes such as nicotinamide-adenine-dinucleotide-phosphate [NAD(P)H] quinone oxidoreductase (NQO1) without modifying oxidation enzymes. The induction of these protective enzymes appears to be mediated by genetic regulatory elements in their promoter regions known as the antioxidant response element (ARE). The aim of this study was to identify, through an in vitro study, which of the 30 fruits and vegetables commonly consumed in Catalonia, Spain, contain MIs of NQO1. We assayed the capacity of extracts of these fruits and vegetables to induce NQO1 [by more than 1.5-fold: ratio of induction (cells treated/control) >1.5, 8-mg/ml dose] in two murine hepatoma cell lines: Hepa 1c1c7 and BPrC1, a modified cell line that possesses a nonfunctional aryl hydrocarbon receptor nuclear translocator system and is thus nonresponsive to bifunctional inducers. We also used a third cell line, papiloma (PE) murine keratinocytes, a stably transfected cell line with an ARE-luc+ plasmid (AREPE cell line) for verifying induction through the ARE with a simple luminescence screening assay. Broccoli (Hepa 1c1c7, ratio=5.5; BPrC1, ratio=2.3), calcot (Allium cepa L.) (Hepa 1c1c7, ratio=4.7; BPrC1, ratio=.5), green onion (Hepa 1c1c7, ratio=4.6; BPrC1, ratio=2), green cabbage (Hepa 1c1c7, ratio=3.6; BPrC1, ratio=2.7), purple cabbage (Hepa 1c1c7, ratio=3.4; BPrC1, ratio=2), and black cabbage (Hepa 1c1c7, ratio=3; BPrC1, ratio=3) were active NQO1 inducers in both murine hepatoma cell lines. Extracts from broccoli (ratio=3.5), calcot (ratio=4.8), cauliflower (ratio=4.2), cabbage (ratio=2.2), green onion (ratio=3.2), green cabbage (ratio=3.6), black cabbage (ratio=4.5), and purple cabbage (ratio=3.7) were confirmed to contain MIs in the AREPE cell line. These results are very similar to those described for vegetables consumed in the United States, with the exception of calcot, which is common in Catalonia but is not grown or consumed widely in the United States.
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PMID:Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in Catalonia, Spain. 1609 Oct 4