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Bannai, Kiyoshi; Kurozumi, Seizi

doi:10.5059/yukigoseikyokaishi.42.794

Cited by 12 publications

(9 citation statements)

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“…While the addition of 500 M to 1 mM of DEM to the culture medium depletes the intracellular stores of GSH significantly, the addition of 100 M DEM only diminishes the GSH level minimally, and then its level increases as a result of induced system x c Ϫ activity (26). As expected, the defect in inducible ؊ or GSH in Nrf2-deficient macrophages.…”

Section: Impaired Induction Of Antioxidative Stress Proteins In Nrf2-mentioning

confidence: 49%

“…Induction of the Cystine Transporter x c Ϫ System Is Defective in Nrf2-deficient Cells-Because oxidative stress agents transcriptionally induce system x c Ϫ activity in macrophages (20,26), the stress induction of system x c Ϫ activity in nrf2-null mutant cells was examined next (Fig. 2A).…”

Section: Impaired Induction Of Antioxidative Stress Proteins In Nrf2-mentioning

confidence: 99%

“…A170 has a structural domain that interacts with ubiquitin (24) and PKC- (25). Electrophilic agents, such as diethylmaleate (DEM), and other oxidative stress agents have been reported to induce the proteins HO-1, A170, MSP23, and system x c Ϫ activity in peritoneal macrophages (20) and fibroblasts (26). To determine whether these antioxidant stress proteins are also under the regulation of Nrf2, we examined in this study the electrophilic induction of this group of genes in peritoneal macrophages from the nrf2-null mutant mouse.…”

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confidence: 99%

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Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages

Ishii¹,

Itoh²,

Takahashi

et al. 2000

Journal of Biological Chemistry

1,319

978

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Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione Stransferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophileand oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x c Ϫ ) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x c Ϫ activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wideranging metabolic response to oxidative stress.

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Section: Impaired Induction Of Antioxidative Stress Proteins In Nrf2-mentioning

confidence: 49%

Section: Impaired Induction Of Antioxidative Stress Proteins In Nrf2-mentioning

confidence: 99%

mentioning

confidence: 99%

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Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages

Ishii¹,

Itoh²,

Takahashi

et al. 2000

Journal of Biological Chemistry

1,319

978

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“…On the other hand, cysteine is very sparse in most cells because of lack of synthetic activity. Therefore, it is necessary for most cells to take up cysteine from the medium, and it has been shown that the intracellular cysteine content is a rate-limiting factor in GSH synthesis [23,24]. Cysteine is easily autoxidized to cystine in extracellular £uid, whereas cystine is rapidly reduced to cysteine once it enters the cells [16].…”

Section: Discussionmentioning

confidence: 99%

High concentration of glucose causes impairment of the function of the glutathione redox cycle in human vascular smooth muscle cells

et al. 1998

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We demonstrated that high glucose reduced H P O P scavenge activity in human vascular smooth muscle cells. In the cells exposed to high glucose, the intracellular glutathione content decreased, although the NADPH content was unchanged. The rate of uptake of cystine, which is a rate-limiting precursor of the glutathione synthesis, decreased in the high glucose group compared with the control group. These decreases were shown to be dependent on glucose concentration. It was suggested that high glucose causes impairment of the function of the glutathione redox cycle in human vascular smooth muscle cells, resulting in reduced H P O 2 scavenge activity.z 1998 Federation of European Biochemical Societies.

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“…Five hours later the cells were shocked with 15% (wt/vol) glycerol for 2 min and then allowed to recover for 16-18 hr. The cells from each 10 10-cm dish for (galactosidase assay, and the remaining cells were distributed among the wells of three 24-well plates containing 1.5 ml of medium per well. After 3-4 hr the cells were treated with three or more concentrations of inducers dissolved in either dimethyl sulfoxide (DMSO) or water (arsenicals and metal salts).…”

Section: Methodsmentioning

confidence: 99%

Chemical and molecular regulation of enzymes that detoxify carcinogens.

Prestera

Holtzclaw

Zhang

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

384

271

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Inductions of detoxication (phase 2) enzymes, such as glutathione transferases and NAD(P)H:(quinoneacceptor) oxidoreductase, are a major mechanism for protecting animals and their cells against the toxic and neoplastic effects of carcinogens. These inductions result from enhanced transcription, and they are evoked by diverse chemical agents: oxidizable diphenols and phenylenediamines; Michael reaction acceptors; organic isothiocyanates; other electrophiles-e.g., alkyl and aryl halides; metal ions-e.g., HgCl2 and CdCl2; trivalent arsenic derivatives; vicinal dimercaptans; organic hydroperoxides and hydrogen peroxide; and 1,2-dithiole-3-thiones. The molecular mechanisms of these inductions were analyzed with the help of a construct containing a 41-bp enhancer element derived from the 5' upstream region of the mouse liver glutathione transferase Ya subunit gene ligated to the 5' end of the isolated promoter region of this gene, and inserted into a plasmid containing a human growth hormone reporter gene. When this construct was transfected into Hep G2 human hepatoma cells, the concentrations of 28 compounds (from the above classes) required to double growth hormone production, and the concentrations required to double quinone reductase specific activities in Hepa lclc7 cells, spanned a range of four orders of magnitude but were closely linearly correlated. Six compounds tested were inactive in both systems. A 26-bp subregion of the above enhancer oligonucleotide (containing the two tandem "AP-1-like" sites but lacking the preceding ETS protein binding sequence) was considerably less responsive to the same inducers. We conclude that the 41-bp enhancer element mediates most, if not all, of the phase 2 enzyme inducer activity of all of these widely different classes of compounds.acceptors, diphenols, quinones, isothiocyanates, peroxides, vicinal dimercaptans, heavy metals, arsenicals, and others (12)(13)(14). With few exceptions these agents are electrophiles (or can be converted to electrophiles by metabolism), and accordingly, many of these inducers are substrates for glutathione transferases (13).The molecular basis of the regulation of phase 2 enzyme inductions has been analyzed by deletions of the 5' upstream regulatory regions of glutathione transferase Ya subunit genes and QR genes after transfection of cells with chloramphenicol acetyltransferase (CAT) constructs (3,(15)(16)(17). The sequences of the upstream enhancer elements of the mouse and rat liver glutathione transferase Ya subunit genes that respond to the few inducers tested are very similar and have been termed the electrophile-responsive element (EpRE) (18) and the antioxidant-responsive element (ARE) (19), respectively. These elements (Fig. 1) are contained within a 41-nt segment located between base pairs -754 and -714 in the mouse, and -722 and -682 in the rat Ya gene. The critical DNA sequences responsive to monofunctional inducers appear to be the TGACAT/AT/AGC regions, which resemble AP-1 binding sites (20). Similar enhancer sequences ha...

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Cited by 12 publications

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Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages

Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages

High concentration of glucose causes impairment of the function of the glutathione redox cycle in human vascular smooth muscle cells

Chemical and molecular regulation of enzymes that detoxify carcinogens.

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