Selenium deficiency activates mouse liver Nrf2–ARE but vitamin E deficiency does not

Burk, Raymond F.; Hill, Kristina E.; Nakayama, Akihiro; Mostert, Volker; Levander, Ximena A.; Motley, Amy K.; Johnson, Dale G.; Johnson, Jeffrey A.; Freeman, Michael L.; Austin, Lori M.

doi:10.1016/j.freeradbiomed.2008.01.016

Cited by 81 publications

(58 citation statements)

References 37 publications

(44 reference statements)

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“…36). A link between NRF2 and selenium metabolism has been characterized, but this depended on the tissue analyzed (51,52). In HEK293 cells, we observed very little regulation of selenoprotein mRNA levels as a function of selenium bioavailability or oxidative stress, even though selenoprotein expression was modulated dramatically, indicating a specific translational control of this family of proteins in the cell line analyzed.…”

Section: Discussionmentioning

confidence: 72%

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Touat-Hamici

Legrain

Bulteau

et al. 2014

Journal of Biological Chemistry

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Background: Selenoproteins are important enzymes involved in antioxidant defense, redox homeostasis, and signaling. Results: We report that, in HEK293 cells, several selenoproteins are selectively up-regulated in response to H 2 O 2 treatment. Conclusion: We identify a novel translational control mechanism for selenoproteome regulation. Significance: Antioxidant selenoproteins are regulated by oxidative stress when selenium is limiting.

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Section: Discussionmentioning

confidence: 72%

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Touat-Hamici

Legrain

Bulteau

et al. 2014

Journal of Biological Chemistry

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“…A simultaneous disruption of Trsp and Nrf2 abolished the induction of phase II enzymes, thus, verifying the role of Nrf2 in responding to the loss of selenoproteins [52]. The ARE-driven reporter gene activity in ARE-reporter mice fed a selenium-deficient diet was strongly enhanced compared to mice fed the control diet [9]. In addition, the increased GST and NQO1 activity observed in selenium-deficient wild type mice was not detectable in Nrf2 -/-mice [9].…”

Section: Introductionmentioning

confidence: 72%

“…The establishment of a marginal selenium-deficiency is in contrast to most of the other studies investigating the effects of either high selenium supplementation or severe selenium-deficiency. Also Burk and colleagues, who provided the first direct link between dietary selenium-deficiency and Nrf2 activation, compared mice fed either a completely seleniumdeficient or a -supplemented diet with 0.25 mg sodium selenite per kg [9]. Under selenium-deficient conditions, ARE-driven reporter gene activity as well as GST and NQO1 activity were strongly increased in the liver of wild-type mice but were unchanged in Nrf2 -/-mice.…”

Section: Discussionmentioning

confidence: 99%

“…The ARE-driven reporter gene activity in ARE-reporter mice fed a selenium-deficient diet was strongly enhanced compared to mice fed the control diet [9]. In addition, the increased GST and NQO1 activity observed in selenium-deficient wild type mice was not detectable in Nrf2 -/-mice [9]. This provided the first direct link between dietary selenium-deficiency and Nrf2 activation.…”

Section: Introductionmentioning

confidence: 86%

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Nrf2 target genes are induced under marginal selenium-deficiency

et al. 2010

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A suboptimal selenium supply appears to prevail in Europe. The current study, therefore, was focused on the changes in gene expression under a suboptimal selenium intake. Previous microarray analyses in the colon of mice fed either a selenium-adequate or a moderately deficient diet revealed a change in genes of several pathways. Severe selenium-deficiency has been found previously to influence Nrf2-regulated genes of the adaptive response. Since the previous pathway analyses were done with a program not searching for Nrf2 target genes, respective genes were manually selected and confirmed by qPCR. qPCR revealed an induction of phase II (Nqo1, Gsts, Sult1b1 and Ugt1a6) and antioxidant enzymes (Hmox1, Mt2, Prdx1, Srxn1, Sod1 and Gclc) under the selenium-poor diet, which is considered to compensate for the loss of selenoproteins. The strongest effects were observed in the duodenum where preferentially genes for antioxidant enzymes were up-regulated. These also include the mRNA of the selenoproteins TrxR1 and GPx2 that would enable their immediate translation upon selenium refeeding. The down-regulation of Gsk3b in moderate selenium-deficiency observed in the previous paper provides a possible explanation for the activation of the Nrf2 pathway, because inhibition of GSK3b results in the nuclear accumulation of Nrf2.

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“…These findings indicate that selenium deficiency causes oxidative conditions in the liver, thus leading to activation of transcriptional factor AP-1-mediated induction of such stress responsive enzymes. With respect to selenium-deficient animals, Burk et al (2008) found the increase in Nrf2/ARE system and its regulatory enzymes of NQO1, HO-1 and GST. However, such an increase in the antioxidant responsive system did not occur with vitamin E deficiency.…”

Section: Pb As An Inducer Of Ho-1 In Selenium-deficient Animalsmentioning

confidence: 94%

Chemical-induced coordinated and reciprocal changes in heme metabolism, cytochrome P450 synthesis and others in the liver of humans and rodents

2016

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-A wide variety of drugs and chemicals have been shown to produce induction and inhibition of heme-metabolizing enzymes, and of drug-metabolizing enzymes, including cytochrome P450s (P450s, CYPs), which consist of many molecular species with lower substrate specificity. Such chemically induced enzyme alterations are coordinately or reciprocally regulated through the same and/or different signal transductions. From the toxicological point of view, these enzymatic changes sometimes exacerbate inherited diseases, such as precipitation of porphyrogenic attacks, although the induction of these enzymes is dependent on the animal species in response to the differences in the stimuli of the liver, where they are also metabolized by P450s. Since P450s are hemoproteins, their induction and/or inhibition by chemical compounds could be coordinately accompanied by heme synthesis and/or inhibition. This review will take a retrospective view of research works carried out in our department and current findings on chemical-induced changes in hepatic heme metabolism in many places, together with current knowledge. Specifically, current beneficial aspects of induction of heme oxygenase-1, a rate-limiting heme degradation enzyme, and its relation to reciprocal and coordinated changes in P450s, with special reference to CYP2A5, in the liver are discussed. Mechanistic studies are also summarized in relation to current understanding on these aspects. Emphasis is also paid to an example of a single chemical compound that could cause various changes by mediating multiple signal transduction systems. Current toxicological studies have been developing by utilizing a sophisticated "omics" technology and survey integrated changes in the tissues produced by the administration of a chemical, even in time-and dose-dependent manners. Toxicological studies are generally carried out step by step to determine and elucidate mechanisms produced by drugs and chemicals. Such approaches are correct; however, current "omics" technology can clarify overall changes occurring in the cells and tissues after treating animals with drugs and chemicals, integrate them and discuss the results. In the present review, we will discuss chemical-induced similar changes of heme synthesis and degradation, and of P450s and finally convergence to similar or different directions.

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Selenium deficiency activates mouse liver Nrf2–ARE but vitamin E deficiency does not

Cited by 81 publications

References 37 publications

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Nrf2 target genes are induced under marginal selenium-deficiency

Chemical-induced coordinated and reciprocal changes in heme metabolism, cytochrome P450 synthesis and others in the liver of humans and rodents

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