TY - JOUR A1 - Baier, Heiko A1 - Kelling, Alexandra A1 - Schilde, Uwe A1 - Holdt, Hans-Jürgen T1 - Investigation of the Catalytic Activity of a 2-Phenylidenepyridine Palladium(II) Complex Bearing 4,5-Dicyano-1,3-bis(mesityl)imidazol-2-ylidene in the Mizoroki-Heck Reaction JF - Zeitschrift für anorganische und allgemeine Chemie N2 - The phenylidenepyridine (ppy) palladacycles [PdCl(ppy)(IMes)] (4) [IMes = 1,3-bis(mesityl) imidazol-2-ylidene] and [PdCl(ppy){(CN)(2)IMes}] (6) [(CN)(2)IMes = 4,5-dicyano-1,3-bis(mesityl) imidazol-2-ylidene] were prepared by facile two step syntheses, starting with the reaction of palladium(II) chloride with 2-phenylpyridine followed by subsequent addition of the NHC ligand to the precatalyst precursor [PdCl(ppy)](2). Suitable crystals for the X-ray analysis of the complexes 4 and 6 were obtained. It was shown that 6 has a shorter NHC-palladium bond than the IMes complex 4. The difference of the palladium carbene bond lengths based on the higher pi-acceptor strength of (CN)(2)IMes in comparison to IMes. Thus, (CN)(2)IMes should stabilize the catalytically active central palladium atom better than IMes. As a measure for the pi-acceptor strength of (CN)(2)IMes compared to IMes, the selone (CN)(2)IMes center dot Se (7) was prepared and characterized by Se-77-NMR spectroscopy. The pi-acceptor strength of 7 was illuminated by the shift of its Se-77-NMR signal. The Se-77-NMR signal of 7 was shifted to much higher frequencies than the Se-77-NMR signal of IMes center dot Se. Catalytic experiments using the Mizoroki-Heck reaction of aryl chlorides with n-butyl acrylate showed that 6 is the superior performer in comparison to 4. Using complex 6, an extensive substrate screening of 26 different aryl bromides with n-butyl acrylate was performed. Complex 6 is a suitable precatalyst for para-substituted aryl bromides. The catalytically active species was identified by mercury poisoning experiments to be palladium nanoparticles. KW - Carbene ligands KW - Heck reaction KW - Palladium KW - Selenium KW - C-C coupling Y1 - 2016 U6 - https://doi.org/10.1002/zaac.201500625 SN - 0044-2313 SN - 1521-3749 VL - 642 SP - 140 EP - 147 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bornhorst, Julia A1 - Kipp, Anna P. A1 - Haase, Hajo A1 - Meyer, Soeren A1 - Schwerdtle, Tanja T1 - The crux of inept biomarkers for risks and benefits of trace elements JF - Trends in Analytical Chemistry N2 - Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE. KW - Trace elements KW - Copper KW - Zinc KW - Manganese KW - Selenium KW - Biomarker KW - Inductively coupled plasma mass spectrometry KW - Hyphenated techniques KW - Isotope ratios Y1 - 2018 U6 - https://doi.org/10.1016/j.trac.2017.11.007 SN - 0165-9936 SN - 1879-3142 VL - 104 SP - 183 EP - 190 PB - Elsevier CY - Oxford ER - TY - THES A1 - Kipp, Anna Patricia T1 - Selen, Selenoproteine und der Wnt-Signalweg : Regulation der gastrointestinalen Glutathionperoxidase durch β-Catenin und Beeinflussung des Wnt-Signalwegs durch den Selenstatus T1 - Selenium, selenoproteins, and the Wnt pathway : regulation of the gastrointestinal glutathione peroxidase via the Wnt pathway and influence of the selenium status on the activity of the Wnt pathway N2 - Das seit 1957 als essentiell klassifizierte Spurenelement Selen vermittelt seine Funktion hauptsächlich durch seinen Einbau in Selenoproteine in Form der 21. proteinogenen Aminosäure Selenocystein. Insgesamt wurden 25 humane Gene für Selenoproteine identifiziert, deren genaue Funktion häufig noch nicht bekannt ist. Selen ist das einzige Mitglied aus der Gruppe der Mikronährstoffe, für das nach wie vor eine antikanzerogene Funktion vor allem in Bezug auf Darmkrebs postuliert wird. Die Grundlage dafür liefert eine Interventionsstudie, bei der 1.312 Probanden für 4,5 Jahre mit 200 μg Selen/Tag supplementiert wurden. Dies resultierte in einer Senkung der Gesamtkrebsmortalität um 50 %. Die Fragen einer optimalen Selenzufuhr, die nicht nur den Bedarf deckt, sondern auch die Entfaltung der antikanzerogenen Wirkung von Selen gewährleistet und die zugrunde liegenden molekularen Mechanismen sind noch ungeklärt. Zudem liegt die Selenzufuhr bei einem Großteil der europäischen Bevölkerung unter den Empfehlungen. Deshalb wurden in der vorliegenden Arbeit vier Wochen alte Mäuse für sechs Wochen marginal defizient (0,086 mg/kg Futter) bzw. selenadäquat (0,15 mg/kg Futter) gefüttert. Dieser geringe Unterschied im Selengehalt resultierte in einer Senkung des Plasmaselenspiegels der selenarmen Tiere auf 13 % und der GPx-Aktivität in der Leber auf 35 %. Zunächst wurde der Einfluss von Selen auf die globale Genexpression im murinen Colon mittels Microarray untersucht. Von den im Colon exprimierten Selenoproteinen reagierte die mRNA von SelW, SelH, GPx1 und SelM im Selenmangel besonders deutlich mit Expressionsverlust. Da diese Selenoproteine nicht nur im Colon, sondern auch in Leukozyten reguliert waren, sind sie auch als humane Biomarker für die in dieser Studie gewählte Schwankung des Selengehalts geeignet. Des Weiteren wurde auf Basis der Microarraydaten eine Signalweganalyse durchgeführt, die der Identifizierung krebsrelevanter Signalwege diente, um mögliche molekularbiologische Erklärungsansätze für die Rolle von Selen im Krebsgeschehen zu finden. Es zeigte sich, dass die mRNA von Schlüsselgenen des Wnt-Signalwegs wie β-Catenin, Gsk3β, Dvl2, Tle2, Lef1 und c-Myc auf Schwankungen des Selengehalts reagiert. Vor allem die Induktion von c-Myc, einem Zielgen des Wnt-Signalwegs, deutet darauf hin, dass dieser im Selenmangel tatsächlich aktiver ist als bei selenadäquater Versorgung. Ein weiterer möglicher Erklärungsansatz für die postulierte präventive Funktion von Selen gegenüber Darmkrebs ist die gastrointestinale Glutathionperoxidase (GPx2), die physiologisch in den proliferierenden Zellen des Kryptengrunds exprimiert wird. Die Regulation dieses Enzyms durch den Wnt-Signalweg, der ebenfalls in proliferierenden Zellen aktiv ist, konnte mittels Reportergenanalyse und endogen auf mRNA- und Proteinebene in Zellkultur gezeigt werden. Die Aktivierung verkürzter Promotorkonstrukte und die Mutation eines potentiellen Bindeelements identifizierten den für die Bindung von TCF und β-Catenin verantwortlichen Bereich. Als Zielgen des Wnt-Signalwegs scheint GPx2 zu den an Proliferationsprozessen beteiligten Genen zu gehören, was unter physiologischen Bedingungen die Aufrechterhaltung des intestinalen Epithels gewährleistet. Bei der Entstehung intestinaler Tumore, die in der Initiationsphase zu über 90 % mit einer konstitutiven Aktivierung des Wnt-Signalwegs einhergeht, wirkt GPx2 möglicherweise prokanzerogen. Die genaue Funktion von GPx2 während der Kanzerogenese bleibt weiter zu untersuchen. N2 - Suboptimal selenium (Se) status has been suggested to be associated with a higher risk of developing various cancers, especially colon cancer. In mammals, Se exerts its functions through selenoproteins into which it is incorporated as selenocysteine. Since the function of many selenoproteins has not been identified the underlying mechanisms of the anti-carcinogenic function of Se remains unclear. Therefore, mice were fed either a marginal Se-deficient diet (0.086 mg Se/kg) or a Se-adequate diet (0.15 mg Se/kg) for six weeks. The plasma Se level was reduced to 13 % in the Se-deficient group while GPx activity in the liver was reduced to 35 %. The influence of Se on the global gene expression pattern was analysed using microarray technology. Among selenoproteins SelW, GPx1, SelH and SelM were consistently lower expressed in animals fed with the Se-deficient diet. As the mRNA of these genes was regulated in leucocytes as well, they are possible new biomarkers for the Se status in human studies. In addition, pathway analysis revealed that the cancer-relevant Wnt pathway was affected by the Se status, indicated by changes in the mRNA expression of key proteins like β-catenin, Gsk3β, Dvl2, Tle2, Lef1 and the Wnt target gene c-Myc. The regulation of these genes by Se points to a slightly increased basal activity level of the Wnt pathway in the Se poor state and may therefore contribute to the higher cancer risk in a marginal Se deficiency. Another possible explanation for anti-carcinogenic effects of Se is the gastrointestinal glutathione peroxidase GPx2, a selenoprotein predominantly expressed in proliferating cells at the crypt grounds of the intestine. The regulation of GPx2 via the Wnt pathway was confirmed by reporter gene experiments and by analysing endogenous GPx2 expression on the mRNA as well as on the protein level in different cell culture systems. Shortened promoter constructs and the mutation of a potential TCF binding element identified the area responsible for β-catenin/TCF binding. GPx2 is the first selenoprotein identified as a target of the Wnt pathway. This finding suggests a function of GPx2 in the maintenance of normal renewal of the intestinal epithelium as well as in cancer development. KW - Selen KW - Biomarker KW - Wnt-Signalweg KW - GPx2 KW - Selenium KW - biomarker KW - Wnt pathway KW - GPx2 Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-30484 ER - TY - JOUR A1 - Rohn, Isabelle A1 - Kroepfl, Nina A1 - Aschner, Michael A1 - Bornhorst, Julia A1 - Kuehnelt, Doris A1 - Schwerdtle, Tanja T1 - Selenoneine ameliorates peroxide-induced oxidative stress in C. elegans JF - Journal of trace elements in medicine and biology N2 - Scope: Selenoneine (2-selenyl-N-alpha, N-alpha, N-alpha-trimethyl-L-histidine), the selenium (Se) analogue of the ubiquitous thiol compound and putative antioxidant ergothioneine, is the major organic selenium species in several marine fish species. Although its antioxidant efficacy has been proposed, selenoneine has been poorly characterized, preventing conclusions on its possible beneficial health effects. Methods and results: Treatment of Caenorhabditis elegans (C. elegans) with selenoneine for 18 h attenuated the induction of reactive oxygen and nitrogen species (RONS). However, the effect was not immediate, occurring 48 h post-treatment. Total Se and Se speciation analysis revealed that selenoneine was efficiently taken up and present in its original form directly after treatment, with no metabolic transformations observed. 48 h posttreatment, total Se in worms was slightly higher compared to controls and no selenoneine could be detected. Conclusion: The protective effect of selenoneine may not be attributed to the presence of the compound itself, but rather to the activation of molecular mechanisms with consequences at more protracted time points. KW - Selenoneine KW - Caenorhabditis elegans KW - Selenium KW - Oxidative stress Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.05.012 SN - 0946-672X VL - 55 SP - 78 EP - 81 PB - Elsevier GMBH CY - München ER - TY - JOUR A1 - Solovyev, Nikolay A1 - Prakash, N. Tejo A1 - Bhatia, Poonam A1 - Prakash, Ranjana A1 - Drobyshev, Evgenii J. A1 - Michalke, Bernhard T1 - Selenium-rich mushrooms cultivation on a wheat straw substrate from seleniferous area in Punjab, India JF - Journal of trace elements in medicine and biology N2 - Intensive rice-wheat cultivation cycle in Northern belt of India in general and in the State of Punjab in particular results in large volumes of straw and other post-harvest residue annually. The agricultural area, bordering the districts of Nawanshahr and Hoshiarpur, is popularly known as the seleniferous belt of India. The agri-residues, generated in seleniferous region of this state, are observed to contain significantly high concentration of selenium (Se). The present study was aimed to evaluate the Se uptake by different mushroom species: Pleurotus sajorcaju, Pleurotus ostreatus, Pleurotus citrinopileatus, Agaricus bisporus, and Volvariella volvacea, cultivated on Se-rich wheat and paddy straw from the seleniferous region. Wheat (Pleurotus species and A. bisporus) and paddy straw (V. volvacea) was inoculated with the mycelium spawn and left for 7-20 days, depending on the species, to grow. Control mushrooms were grown analogously using the agricultural residues from non-seleniferous area of the State of Punjab. All fruiting bodies were collected and analyzed in triplicate. Se was quantified using inductively coupled plasma sector field mass spectrometry. The Se accumulation was high in all species under study, being the highest in A. bisporus (1396 mu g/g vs. 46.8 mu g/g in controls - dry weight) and V. volvacea (231 mu g/g vs. 3.77 mu g/g - dry weight). The observed biological efficiency and total yield for all mushroom species showed good and unaltered productivity in Se-rich conditions, if compared to the controls. The Se-rich mushrooms can be prospective Se-supplements sourcing and biofortified foods, providing readily bioavailable and accessible Se for the diets deficient of this biologically essential element. KW - Selenium KW - Mushrooms KW - Cultivation KW - Bioaccumulation KW - Seleniferous area KW - Supplements Y1 - 2018 U6 - https://doi.org/10.1016/j.jtemb.2018.07.027 SN - 0946-672X VL - 50 SP - 362 EP - 366 PB - Elsevier CY - Jena ER - TY - JOUR A1 - Speckmann, Bodo A1 - Schulz, Sarah A1 - Hiller, Franziska A1 - Hesse, Deike A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Geisel, Juergen A1 - Obeid, Rima A1 - Grune, Tilman A1 - Kipp, Anna Patricia T1 - Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice JF - The journal of nutritional biochemistry N2 - The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc. KW - Selenium KW - DNA methylation KW - Liver KW - Lipogenesis KW - Srebf1 Y1 - 2017 U6 - https://doi.org/10.1016/j.jnutbio.2017.07.002 SN - 0955-2863 SN - 1873-4847 VL - 48 SP - 112 EP - 119 PB - Elsevier CY - New York ER -