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F R Dunshea - One of the best experts on this subject based on the ideXlab platform.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, F R Dunshea, Kate Howell, Ken Ng
    Abstract:

    Abstract The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5 weeks with control diet (0.15 μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1 μg Se/g feed). The mRNA expression levels were found to be significantly ( P P A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, Kate Howell, F R Dunshea
    Abstract:

    The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5weeks with control diet (0.15μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1μg Se/g feed). The mRNA expression levels were found to be significantly (P<0.01) up-regulated by 1.65-fold and 2.3-fold for GPx-1 and GPx-2, respectively, but were not significantly different for TrxR-1 and SeP between the 2 diet treatments. The up-regulation of GPx-1 mRNA expression was consistent with GPX-1 activity level, which was significantly (P<0.05) increased by 1.77-fold in rats fed with the Se-enriched diet compared to the control diet. The results showed that selenised A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

Tebo Maseko - One of the best experts on this subject based on the ideXlab platform.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, F R Dunshea, Kate Howell, Ken Ng
    Abstract:

    Abstract The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5 weeks with control diet (0.15 μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1 μg Se/g feed). The mRNA expression levels were found to be significantly ( P P A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, Kate Howell, F R Dunshea
    Abstract:

    The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5weeks with control diet (0.15μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1μg Se/g feed). The mRNA expression levels were found to be significantly (P<0.01) up-regulated by 1.65-fold and 2.3-fold for GPx-1 and GPx-2, respectively, but were not significantly different for TrxR-1 and SeP between the 2 diet treatments. The up-regulation of GPx-1 mRNA expression was consistent with GPX-1 activity level, which was significantly (P<0.05) increased by 1.77-fold in rats fed with the Se-enriched diet compared to the control diet. The results showed that selenised A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

Ken Ng - One of the best experts on this subject based on the ideXlab platform.

Kate Howell - One of the best experts on this subject based on the ideXlab platform.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, F R Dunshea, Kate Howell, Ken Ng
    Abstract:

    Abstract The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5 weeks with control diet (0.15 μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1 μg Se/g feed). The mRNA expression levels were found to be significantly ( P P A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

  • selenium enriched agaricus bisporus increases expression and activity of Glutathione Peroxidase 1 and expression of Glutathione Peroxidase 2 in rat colon
    Food Chemistry, 2014
    Co-Authors: Tebo Maseko, Kate Howell, F R Dunshea
    Abstract:

    The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione Peroxidase-1 (GPx-1), gastrointestinal specific Glutathione Peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5weeks with control diet (0.15μg Se/g feed) or Se-enriched diet fortified with selenised mushroom (1μg Se/g feed). The mRNA expression levels were found to be significantly (P<0.01) up-regulated by 1.65-fold and 2.3-fold for GPx-1 and GPx-2, respectively, but were not significantly different for TrxR-1 and SeP between the 2 diet treatments. The up-regulation of GPx-1 mRNA expression was consistent with GPX-1 activity level, which was significantly (P<0.05) increased by 1.77-fold in rats fed with the Se-enriched diet compared to the control diet. The results showed that selenised A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon.

Regina Brigeliusflohe - One of the best experts on this subject based on the ideXlab platform.

  • Glutathione Peroxidase 2 a selenoprotein exhibiting a dual personality in preventing and promoting cancer
    2016
    Co-Authors: Regina Brigeliusflohe, Anna P Kipp
    Abstract:

    GPx2 is mainly expressed in the intestine but also up-regulated in several cancer types. Being a selenoprotein and a target of the transcription factor Nrf2, it was first proposed to protect from tumor development. However, it turned out that the picture is much more complex. GPx2 is not only regulated by Nrf2, but also by β-catenin and the Wnt pathway, ΔNp63, and NKX3.1, which are pathways involved in the regulation of proliferative and survival processes. Accordingly, GPx2 was also found to enhance proliferation and to inhibit apoptosis. These are important functions required to maintain homeostasis in the healthy intestine. However, acting in cancer cells, they will promote the progression of the disease, as confirmed in several models of cancer and by a decrease of tumor development in Gpx2 knockout mice. In contrast, if carcinogenesis is driven by inflammation, GPx2 rather acts protective. The recent identification of STAT3 as an additional transcription factor inducing GPx2 might explain the up-regulation of GPx2 in inflammation and point to a role of GPx2 in tissue regeneration and wound healing. Thus, in accordance with the different pathways regulating its expression, GPx2 can act anti- and pro-carcinogenic depending on the tumor model and stage of cancer. Whereas it can inhibit initiation, it supports tumor growth, if a cancer cell has been established.

  • deletion of Glutathione Peroxidase 2 inhibits azoxymethane induced colon cancer development
    PLOS ONE, 2013
    Co-Authors: Mike F Muller, Regina Brigeliusflohe, Simone Florian, Stefanie Pommer, M Osterhoff, Steven R Esworthy, Fongfong Chu, Anna P Kipp
    Abstract:

    The selenoprotein Glutathione Peroxidase-2 (GPx2) appears to have a dual role in carcinogenesis. While it protected mice from colon cancer in a model of inflammation-triggered carcinogenesis (azoxymethane and dextran sodium sulfate treatment), it promoted growth of xenografted tumor cells. Therefore, we analyzed the effect of GPx2 in a mouse model mimicking sporadic colorectal cancer (azoxymethane-treatment only). GPx2-knockout (KO) and wild-type (WT) mice were adjusted to an either marginally deficient (−Se), adequate (+Se), or supranutritional (++Se) selenium status and were treated six times with azoxymethane (AOM) to induce tumor development. In the −Se and ++Se groups, the number of tumors was significantly lower in GPx2-KO than in respective WT mice. On the +Se diet, the number of dysplastic crypts was reduced in GPx2-KO mice. This may be explained by more basal and AOM-induced apoptotic cell death in GPx2-KO mice that eliminates damaged or pre-malignant epithelial cells. In WT dysplastic crypts GPx2 was up-regulated in comparison to normal crypts which might be an attempt to suppress apoptosis. In contrast, in the +Se groups tumor numbers were similar in both genotypes but tumor size was larger in GPx2-KO mice. The latter was associated with an inflammatory and tumor-promoting environment as obvious from infiltrated inflammatory cells in the intestinal mucosa of GPx2-KO mice even without any treatment and characterized as low-grade inflammation. In WT mice the number of tumors tended to be lowest in +Se compared to −Se and ++Se feeding indicating that selenium might delay tumorigenesis only in the adequate status. In conclusion, the role of GPx2 and presumably also of selenium depends on the cancer stage and obviously on the involvement of inflammation.

  • the selenoproteins gpx2 trxr2 and trxr3 are regulated by wnt signalling in the intestinal epithelium
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Anna P Kipp, Mike F Muller, Eva M Goken, Stefanie Deubel, Regina Brigeliusflohe
    Abstract:

    Abstract Background The Glutathione Peroxidase 2 (GPx2) is expressed at crypt bases of the intestinal epithelium and in tumour tissue. The GPx2 promoter is activated by the Wnt pathway, which might be the reason for the specific expression pattern of GPx2. Together with additional selenoproteins, thioredoxin reductases TrxR2 and TrxR3, which are putative Wnt targets based on microarray analysis, Wnt-dependent GPx2 expression was analysed. Methods Two cell culture models for either an activated (3T3 cells with Wnt3a overexpression) or an inhibited Wnt pathway (HT-29 APC cells) were analysed. To provide physiological relevance, crypt base epithelial cells of the jejunum and colon of mice were compared to cells of the villus or crypt table, respectively. In addition, β-catenin was deleted in crypt base cells ex vivo. Results In cancer cell lines, the endogenous expression of all three selenoproteins was consistently dependent on Wnt pathway activity. Expression was higher in the proliferative crypt compartment, where also the Wnt pathway is active. An inducible knockout of β-catenin in isolated colonic crypt base cells reduced basal GPx2 expression. We, thus, demonstrated the regulation of GPx2 expression by the Wnt pathway in vitro and in vivo. Furthermore, the selenoproteins TrxR2 and TrxR3 have been identified as novel Wnt targets. This may imply a role of GPx2, TrxR2 and TrxR3 in proliferation, apoptosis and, therefore, also during cancer development. General significance Selenium which is essential for the biosynthesis of Wnt-dependent selenoproteins might be important for the renewal of the intestinal epithelium and during carcinogenesis.

  • the yin and yang of nrf2 regulated selenoproteins in carcinogenesis
    International Journal of Cell Biology, 2012
    Co-Authors: Regina Brigeliusflohe, Mike F Muller, Doris Lippmann, Anna P Kipp
    Abstract:

    The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and Glutathione Peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage.

  • Glutathione Peroxidase 2 and its role in cancer
    2011
    Co-Authors: Antje Banning, Anna P Kipp, Regina Brigeliusflohe
    Abstract:

    Glutathione Peroxidase 2 (GPx2) is preferentially expressed in the intestine, but also upregulated in malignant epithelial cells of other organs. Whether this upregulation is beneficial or detrimental for cancer cell growth and thus for the outcome of cancer, is unclear. The localization of GPx2 in the crypt bases of the intestine, where stem cells proliferate under the control of the Wnt pathway, points to a role in the self-renewal of the intestinal mucosa. This assumption is supported by the fact that GPx2 is a target of the Wnt pathway. In GPx2 knockout mice, apoptosis is highly increased in crypt bases corroborating an involvement of GPx2 in mucosal homeostasis. So far, the role of GPx2 appears to be pro-carcinogenic either by supporting cancer cells to escape apoptosis or by directly maintaining proliferation. On the other hand, GPx2 is induced by Nrf2 transcription factor which is generally accepted to induce endogenous defense systems. In addition, GPx2 counteracts COX-2 expression, thereby decreasing inflammation and migration of tumor cells. Collectively, the role of GPx2 may depend on the stage of cancer. GPx2 likely inhibits the initiation of cancer triggered either by oxidative damage or chronic inflammation and might prevent invasiveness and metastasis, but supports progression of established tumors. Evidences for this dual role of GPx2 are presented and discussed.