Twenty-four base pairs of the human antioxidant response element (hARE) are required for high basal transcription NAD(P)H:quinone oxidoreductase 1 (NQO ) gene and its induction in to xenobiotics antioxidants. hARE is a unique cis-element that contains one perfect imperfect AP1 arranged as inverse repeats separated by 3 bp, followed “GC” box. We report here Jun, Fos, Fra, Nrf nuclear factors bind hARE. Overexpression cDNA derived combinations proteins Jun Fos or Fra1 repressed hARE-mediated...

Glutathione (GSH) significantly declines in the aging rat liver. Because GSH levels are partly a reflection of its synthetic capacity, we measured and activity γ-glutamylcysteine ligase (GCL), rate-controlling enzyme synthesis. With age, both catalytic (GCLC) modulatory (GCLM) subunits GCL decreased by 47% 52%, respectively ( P < 0.005). Concomitant with lower subunit levels, also declined 53% 0.05). nuclear factor erythroid2-related 2 (Nrf2) governs basal inducible GCLC GCLM expression...

The antioxidant response element (ARE) and transcription factor Nrf2 regulate basal expression induction of NAD(P)H:quinone oxidoreductase-1 (NQO1) other detoxifying genes. Under normal conditions, is targeted for proteasomal degradation by INrf2. Oxidative stress causes release from translocates to the nucleus, binds ARE, activates gene expression. In this study, we demonstrate that protein kinase C (PKC) plays a significant role in regulation ARE-mediated NQO1 t-butylhydroquinone....

Nuclear transcription factor Nrf2 regulates the expression and coordinated induction of a battery genes encoding cytoprotective drug transporter proteins in response to chemical radiation stress. This leads reduced apoptosis, enhanced cell survival, increased resistance. In this study, we investigated role up-regulation antiapoptotic protein Bcl-2 its contribution stress-induced apoptosis survival. Exposure mouse hepatoma (Hepa-1) human hepatoblastoma (HepG2) cells antioxidant...

The antioxidant response element (ARE) and Nrf2 are known to regulate the expression coordinated induction of genes encoding detoxifying enzymes including NAD(P)H:quinone oxidoreductase1 (NQO1) in antioxidants. In this report, we demonstrate that overexpression transcription factor Bach1 Hep-G2 cells negatively regulated NQO1 gene t-BHQ. Bandshift supershift assays revealed binds ARE as a heterodimer with small Maf proteins but not homodimer or Nrf2. transfection ChIP competed each other...

of NQOl Gene Expression droxyanisole).Mutation the AP1 binding site contained within hARE resulted in loss basal expression and induction by p-naphthoflavone 3-(2)-tert-butyl-4-hydroxyanisole.We also present evidence to show that regulatory proteins from nuclear extracts these cells specifically interact with two are Jun-D C-FOS. EXPERIMENTAL PROCEDURESConstruction NQOl-CAT Recombinant Plasmid-The construction pNQ01CAT1.55,0.837, 0.365, 0.130 has been described previously (16).The NQO1-CAT...

Atherosclerotic lesions preferentially develop in areas of the vasculature exposed to nonlaminar blood flow and low fluid shear stress, whereas laminar high stress are athero-protective. We have identified a set genes including NAD(P)H:quinone oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), ferritin (heavy light chains), microsomal epoxide hydrolase, glutathione S-transferase, γ-glutamylcysteine synthase, whose expression is induced by exposure prolonged physiological levels steady (shear...

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two-electron reductive metabolism and detoxification of quinones their derivatives leading to protection cells against redox cycling oxidative stress. To examine the in vivo role NQO1, NQO1-null mouse was produced using targeted gene disruption. Mice lacking NQO1 expression showed no detectable phenotype were indistinguishable from wild-type mice. However, mice exhibited increased toxicity when administered menadione...

Induction of cytochrome P1-450 has been linked to susceptibility certain chemically induced cancers in mouse and man. Treatment the human cell line MCF-7 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results high levels aryl hydrocarbon (benzo[a]pyrene) hydroxylase (P1-450) activity. This was used isolate a full-length complementary DNA (cDNA) clone. The cDNA is 2566 nucleotides length, encodes polyadenylated messenger RNA (2.8 kilobases length), continuous reading frame producing protein...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHuman NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxinAnil K. JaiswalCite this: Biochemistry 1991, 30, 44, 10647–10653Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/bi00108a007https://doi.org/10.1021/bi00108a007research-articleACS PublicationsRequest reuse permissionsArticle Views490Altmetric-Citations169LEARN ABOUT...

Abstract Mutations of the breast cancer susceptibility gene 1 (BRCA1), a tumor suppressor, confer an increased risk for breast, ovarian, and prostate cancers. To investigate function BRCA1 gene, we performed DNA microarray confirmatory reverse transcription-PCR analyses to identify BRCA1-regulated expression changes. We found that up-regulates multiple genes involved in cytoprotective antioxidant response, including glutathione S-transferases, oxidoreductases, other genes. Consistent with...

The antioxidant response element (ARE) is known to regulate expression and induction of NQO1, GST Ya, other detoxifying enzyme genes in antioxidants xenobiotics. nuclear transcription factor Nrf2 Nrf1 bind the ARE positively NQO1 Ya genes. In this study, we demonstrate that overexpression small Maf (MafG MafK) proteins negatively ARE-mediated tert-butyl hydroquinone transfected Hep-G2 cells. similar experiments, also repressed Nrf2-mediated up-regulation cells co-transfected with proteins....

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that utilizes NAD(P)H as an electron donor, catalyzing the two-electron reduction and detoxification of quinones their derivatives. NQO1−/− mice deficient in NQO1 activity protein were generated our laboratory (Rajendirane, V., Joseph, P., Lee, Y. H., Kimura, S., Klein-Szanto, A. J. Gonzalez, F. J., Jaiswal, K. (1998) Biol. Chem. 273, 7382–7389). Mice lacking functional gene (NQO1−/−) born normal reproduced adeptly wild-type NQO1+/+...

Monkey kidney COS1 cells transiently transfected with plasmids pMT2-cytochrome P450 1A1 (CYP1A1), reductase (P450 reductase), and pMT2-NAD(P)H:quinone oxidoreductase1 (NQO1 or DT diaphorase), individually in combination, expressed significantly elevated levels of the respective enzyme(s). The were homogenized to break cell membranes without affecting nuclei incubated benzo[a]pyrene (BP) determine role cDNA-encoded enzymes metabolic activation and/or detoxification BP. These studies performed...