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Forschung / Research

Übersicht zu Forschungsarbeiten
Bild von Immunfluoreszenzmikroskop
Foto: Maria Schwarz

Research Projects

1. Interactions of essential trace elements in healthy and diseased elderly (TraceAge)

The homeostasis of trace elements (TE) is affected by nutritional intake, sex, age, and health status. However, interactions of TE under physiological and pathophysiological conditions are poorly characterized. Here we aim to characterize the TE status in women and men of different age (EPIC-Potsdam cohort). To this end, we will measure the TE profiles (Se, Cu, Zn, Mn, Fe, I) from serum along with novel and established biomarkers of the TE status. These data will be combined to establish age- and sex-specific TE fingerprints of German elderly, and help to identify genetic and environmental modifiers. In order to test the relevance of such TE fingerprints, patients with cardiovascular disease during hospitalized rehabilitation (TEhab cohort) will be studied as a paradigm of severe disease with strong changes in mobility and nutrition. To get further mechanistic insights we will study TE profiles and their functional interactions in different tissues from young and old male and female mice under TE-replete and TE-poor conditions. Treatments with TE combinations in mice and C. elegans will identify TE effects on aging, cellular signaling, neurodegeneration, and immune response as well as interactions with drugs and thyroid hormone metabolism. Our results will broaden the understanding of the importance of TE in health and disease. This will provide a basis for better care and future intervention studies to improve the TE status of seniors and to better protect them from degeneration and age-related diseases.

TraceAge-Homepage: https://www.uni-potsdam.de/traceage/Externer Link

Logo TraceAge

Foto: TraceAge

Project Kipp (First funding period): Interactions of trace element profiles with Nrf2 signaling in mice

We hypothesize that age-specific trace element (TE) profiles are modulating the activity of the redox-sensitive transcription factor Nrf2. Vice versa, Nrf2 is supposed to regulate the systemic TE status by changing the expression of TE transport and binding proteins, e.g., in the intestine. To address these points, we aim to conduct feeding experiments in young and old mice fed with adequate or suboptimal amounts of six essential TE, including Cu, Fe, I, Mn, Se, and Zn. In addition, we will establish ‘young-adapted’ and ‘old-adapted’ TE diets, which will mimic the TE status of young and old human EPIC participants. A great advantage over human studies is the availability of murine tissue samples, in which effects of different TE diets will be studied in close collaboration with all experimental groups of the Research Unit. We will focus on the liver and the intestine. Using these tissues, we will correlate TE profiles, TE biomarkers, TE-specific binding proteins, and aging markers with Nrf2 pathway activity. We aim to identify new Nrf2-dependent genes relevant for TE homeostasis and intestinal TE absorp­tion both in young and old mice. To identify the Nrf2-modulated part of TE effects, Nrf2 knockout (KO) mice will be studied in parallel. Potential differences between young and old WT and Nrf2-KO mice may provide an explanation for age-specific TE profiles.

Key publications:

Wolfram T, Schwarz M, Reuß M, Lossow K, Ost M, Klaus S, Schwerdtle T, Kipp AP (2020). N-acetylcysteine as modulator of the essential trace elements copper and zinc, Antioxidants, 9: DOI: 10.3390/antiox9111117Externer Link

Schwarz M, Lossow K, Schirl K, Hackler J, Kopp JF, Renko K, Schwerdtle T, Schomburg L, Kipp AP (2020). Copper interferes with selenoprotein synthesis and activity, Redox Biol., 37: DOI: 10.1016/j.redox.2020.101746Externer Link

Finke H, Winkelbeiner N, Lossow K, Hertel B, Wandt VK, Schwarz M, Pohl G, Kopp JF, Ebert F, Kipp AP, Schwerdtle T (2020). Effects of a cumulative, suboptimal supply of multiple trace elements in mice: trace element status, genomic stability, inflammation and epigenetics, Mol. Nutr. Food Res., 1:e2000325. doi: 10.1002/mnfr.202000325Externer Link

Lossow K, Kopp J, Schwarz M, Finke H, Winkelbeiner NL, Renko K, Meci X, Ott C, Alker W, Hackler J, Grune T, Schomburg L, Haase H, Schwerdtle T, Kipp AP (2020). Ageing affects sex- and organ-specific trace element profiles in mice, Aging US, 12: 13762-13790; https://pubmed.ncbi.nlm.nih.gov/32620712/Externer Link

Hauffe R, Stein V, Chudoba C, Flore T, Rath M, Ritter K, Schell M, Wardelmann K, Deubel S, Kopp JF, Schwarz M, Kappert K, Blüher M, Schwerdtle T, Kipp AP, Kleinridders A (2020). GPx3 dysregulation impacts adipose tissue insulin receptor expression and sensitivity, JCI insight, 5 (11):e136283. doi: https://doi.org/10.1172/jci.insight.136283Externer Link

Baudry J, Kopp JF, Boeing H, Kipp AP, Schwerdtle T, Schulze MB (2019). Changes of trace element status during aging: results of the EPIC-Potsdam cohort study, Eur. J. Nutr., doi: 10.1007/s00394-019-02143-wExterner Link

Schwarz M, Lossow K, Kopp JF, Schwerdtle T, Kipp AP (2019). Crosstalk of Nrf2 with the trace elements selenium, iron, zinc, and copper, Nutrients, Sep 5;11(9); https://pubmed.ncbi.nlm.nih.gov/31491970/Externer Link

Bornhorst J, Kipp AP, Haase H, Meyer S, Schwerdtle T (2017). Trace elements risks and benefits; the crux of biomarkers, Trends in Analytical Chemistry, available online 15 November 2017, https://doi.org/10.1016/j.trac.2017.11.007Externer Link

Kipp AP, Deubel S, Arnér ESJ, Johansson K (2017). Time- and cell-resolved dynamics of Nrf2, HIF and NF-κB in spheroids enriched for cancer stem cells, Redox Biol. 10:403-409. https://doi.org/10.1016/j.redox.2017.03.013Externer Link

Project Kipp (Second funding period): Interactions of trace elements in modulating the immune response during acute and chronic inflammation in mice

In TraceAge I, we could show that supplying mice with low amounts of the trace elements (TE) Cu, Fe, I, Mn, Se, and Zn (TE-) results in growth retardation and increased spleen weight in comparison to mice with adequate TE intake. In line with splenomegaly, serum levels of the inflammatory mediators TNF-α and CRP were increased. Based on our results, it appears that the immune system is very sensitive towards changes in TE intake. During aging, a low-grade systemic inflammation, called inflammaging, has been described. Thus, it is tempting to speculate that older organisms might have another need for TE to cope with inflammation than younger individuals. To address this, we aim to combine our established TE- regime with models of acute and chronic inflammation in young and old mice by applying the DSS model to induce colitis and LPS injection to study systemic inflammation. Besides TE profiles, inflammatory parameters as well as intestinal integrity will be analyzed. Vice versa, it is well-established that TE homeostasis is regulated in a different manner under conditions of inflammation as part of the so-called nutritional immunity. Thus, we aim to understand, how an acute and chronic inflammation affect the TE status and their biomarkers. Both questions will be addressed in mice and complemented with mechanistic studies conducted in cell culture. This project is supposed to provide the basis for considering all six TE in the future to better characterize and eventually improve the health status of humans suffering from acute and chronic inflammation.

 

2. Regulation and function of glutathione peroxidase 2 and other selenoproteins

In a model of inflammation-induced colorectal carcinogenesis, we showed that glutathione peroxidase 2 (GPx2) acts anti-inflammatory, which thus reduces tumor growth. In contrast, GPx2 supported tumor development in a model of sporadic colon cancer. The current project aims to elucidate molecular mechanisms underlying these contradictory effects. In addition, we aim to study further less characterized selenoproteins such as SELENOH.

Key publications:

Koeberle SC, Gollowitzer A, Laoukili J, Kranenburg O, Werz O, Koeberle A, Kipp AP (2020). Distinct and overlapping functions of glutathione peroxidases 1 and 2 in limiting NF-κB-driven inflammation through redox-active mechanisms, Redox Biol., 28:101388. doi: 10.1016/j.redox. 2019.101388Externer Link.

Bertz M, Kühn K, Koeberle SC, Müller MF, Hoelzer D, Thies K, Deubel S, Thierbach R, Kipp AP (2018). Selenoprotein H controls cell cycle progression and proliferation of human colorectal cancer cells, Free Radic. Biol. Med., available online 9 January 2018, https://doi.org/10.1016/j.freeradbiomed.2018.01.010Externer Link

Lennicke C, Rahn J, Wickenhauser C, Lichtenfels R, Müller AS, Wessjohann LA, Kipp AP, Seliger B (2017). Loss of epithelium-specific GPx2 results in aberrant cell fate decisions during intestinal differentiation, Oncotarget, 9:539-552. https://doi.org/10.18632/oncotarget.22640Externer Link

Hiller F, Besselt K, Deubel S, Brigelius-Flohé R, Kipp AP (2015). GPx2 induction is mediated via STAT transcription factors during acute colitis, Inflamm. Bowel Dis. 21:2078-2089. https://doi.org/10.18632/oncotarget.22640Externer Link

Emmink BL, Laoukili J, Kipp AP, Koster J, Govaert KM, Fatrai S, Verheem A, Steller EJA, Brigelius-Flohé R, Jimenez CR, Borel Rinkes IH, Kranenburg O (2014). GPx2 suppression of H2O2 stress links the formation of differentiated tumor mass to metastatic capacity in colorectal cancer, Cancer Res. 74:6717-6730. https://doi.org/10.1158/0008-5472.CAN-14-1645Externer Link

Müller MF, Pommer S, Florian S, Osterhoff M, Esworthy RS, Chu FF, Brigelius-Flohé R, Kipp AP (2013). Deletion of glutathione peroxidase-2 inhibits azoxymethane-induced colon cancer development, PLoS ONE 8: e72055. https://doi.org/10.1371/journal.pone.0072055Externer Link

Brigelius-Flohé R and Kipp A (2009). Glutathione peroxidases in different stages of carcinogenesis, Biochim. Biophys. Acta. 1790:1555-1568. https://doi.org/10.1016/j.bbagen.2009.03.006Externer Link

 

3. Effects of a suboptimal selenium supply

We investigate the effects of a suboptimal selenium supply, which is prevalent in the German population. This is supposed to have negative effects on the immune system as well as on cancer development. The underlying molecular mechanisms need to be elucidated further.

Key publications:

Müller SM, Dawczynski C, Wiest J, Lorkowski S, Kipp AP, Schwerdtle T (2020). Functional biomarkers for the selenium status in a human nutritional intervention study, Nutrients, 12(3). pii: E676. doi: 10.3390/nu12030676Externer Link

Speckmann B, Schulz S, Hiller F, Hesse D, Schumacher F, Kleuser B, Geisel J, Obeid R, Grune T, Kipp AP (2017). Selenium enhances hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice, J. Nutr. Biochem. 48:112-119. https://doi.org/10.1016/j.jnutbio.2017.07.002Externer Link

Lennicke C, Rahn J, Kipp AP, Dojčinović BP, Müller A, Wessjohann LA, Lichtenfels R, Seliger B (2017). Individual effects of different selenocompounds on the hepatic proteome and energy metabolism of mice, Biochim. Biophys. Acta. 1861:3323-3334. https://doi.org/10.1016/j.bbagen.2016.08.015Externer Link

Kipp AP, Strohm D, Brigelius-Flohé R, Schomburg L, Bechthold A, Leschik-Bonnet E, Heseker H (2015). Revised reference values for selenium intake, J. Trace Elem. Med. Biol. 32:195-199. https://doi.org/10.1016/j.jtemb.2015.07.005Externer Link

Hiller F, Oldorff L, Besselt K, Kipp AP (2015). Differential acute effects of selenomethionine and sodium selenite on the severity of colitis, Nutrients 7:2687-2706. https://doi.org/10.3390/nu7042687Externer Link

Geillinger KE, Rathmann D, Köhrle J, Fiamoncini J, Daniel H, Kipp AP (2014). Hepatic metabolite profiles in mice with a suboptimal selenium status, J. Nutr. Biochem. 25:914-922. https://doi.org/10.1016/j.jnutbio.2014.04.003Externer Link

Kipp AP, Banning A, van Schothorst EM, Méplan C, Coort SL, Evelo CT, Keijer J, Hesketh J, Brigelius-Flohé R (2012). Marginal selenium-deficiency down-regulates inflammation-related genes in splenic leukocytes of the mouse, J. Nutr. Biochem. 23:1170-1177. https://doi.org/10.1016/j.jnutbio.2011.06.011Externer Link

26 Publikationen filtern

Die Publikationen filtern

Hervorgehobene Autoren sind Angehörige der Universität Jena.

  1. Connecting concentrations of copper, selenium, and zinc with transcriptomic and proteomic data of well-characterized human colorectal cancer cell lines

    ErscheinungsjahrErschienen in:Journal of Trace Elements in Medicine and Biology C. Meyer, N. Vukelic, J. Mariadason, A. Kipp
    Background: Colorectal cancer (CRC) incidence is associated with lower circulating selenium and zinc and elevated copper concentrations. Moreover, copper and selenium accumulate within tumor tissue, indicating a disturbed homeostasis of these essential trace elements in CRC. Objective: This study aimed to identify associations between CRC characteristics (based on genomic, transcriptomic and proteomic data) and trace element concentrations. Methods: The concentrations of copper, selenium, and zinc were measured in 83 human CRC cell lines and correlated with transcript and protein expression levels to identify trace element-related gene signatures. By using publicly available gene expression data from The Cancer Genome Atlas we investigated the association between those signatures with the survival probability of CRC patients. Results: The CRC cell lines differed in their copper (fold change 7.3), selenium (fold change 6), and zinc (fold change 2.6) concentrations. The concentrations were not associated with genetic or cellular characteristics, except for lower copper concentrations in KRAS mutant cells. Expression levels of known copper- and zinc-related proteins correlated significantly with the respective trace element concentrations, serving as a proxy for trace element concentrations in tumors, and with patient survival. This was not the case for selenium and selenoproteins. In addition, an unbiased approach identified novel high and low copper- and zinc-related gene expression signatures significantly associated with patient's outcome. Conclusion: Herein we identify gene signatures associated with intracellular copper and zinc concentrations in CRC cell lines. Extrapolating these signatures to primary colorectal tumors revealed that they can inform outcome of CRC patients.
    Universitätsbibliographie Jena:
    fsu_mods_00023463Externer Link
  2. Revealing mercury species-specific transfer and toxicity mechanisms in placental trophoblasts

    ErscheinungsjahrErschienen in:Chemosphere: chemistry, biology and toxicology as related to environmental problems V. Michaelis, L. Klemens, A. Thiel, A. Gremme, M. Schwarz, A. Kipp, H. Zischka
    Environmental mercury (Hg) follows a biogeochemical cycle resulting in a variety of Hg species. Therefore, human exposure to the three Hg species inorganic Hg via crops and air, methyl Hg through fish consumption and ethyl Hg due to the use as antiseptic agent in medical applications is a rising concern. Especially pregnant women and their developing fetus present a vulnerable population. However, little is known about its transfer and toxicity in placental barrier building cells. Here, Hg species-specific transfer and toxicity in placental trophoblasts, which are the main cell type involved in nutrient transfer, were investigated by using the established BeWo b30 in vitro model. The transfer of inorganic Hg was much lower compared to the organic Hg species and all three species were able to perturb barrier integrity. This was accompanied by a less pronounced cytotoxicity of HgCl₂ compared to the two organic species. The energy charge value indicated an increase for inorganic Hg and a decrease for organic Hg compounds. Regarding antioxidative defense, inorganic Hg elevated GSSG levels, while organic Hg decreased GSH. Activity of antioxidative defense related enzymes showed a decrease upon Hg species treatment and all three species induced both apoptotic and necrotic cell death.
    Universitätsbibliographie Jena:
    fsu_mods_00018678Externer Link
  3. Improving the selenium supply of vegans and omnivores with Brazil nut butter compared to a dietary supplement in a randomized controlled trial

    ErscheinungsjahrErschienen in:European Journal of Nutrition R. Simon, K. Lossow, D. Pellowski, K. Kipp, M. Achatz, N. Klasen, T. Schwerdtle, C. Dawczynski, A. Kipp
    Purpose: A vegan diet is associated with health benefits but may also lead to inadequate intake of essential nutrients. Due to the lower selenium content in plant-based compared to animal-based foods, many vegans do not reach the recommended selenium intake in Europe. The only plant-based food with high selenium content is the Brazil nut, even though there is also a high variability. Therefore, we investigated the effectiveness of Brazil nut butter compared to a dietary supplement as selenium source to improve the selenium status of vegans and omnivores. Methods: 44 vegans and 42 omnivores were randomly assigned to one of three intervention groups, either receiving placebo or consuming additional 55 µg of selenium daily as Brazil nut butter or supplement for two weeks. Serum selenium concentrations, glutathione peroxidase 3 (GPX3), and selenoprotein P (SELENOP) were measured at baseline and after intervention. Additionally, dietary selenium intake was estimated using a five-day dietary protocol. Results: The estimated selenium intake was significantly lower in vegans compared to omnivores and correlated with all three selenium biomarkers. Independent of the dietary pattern (vegan or omnivore), Brazil nut butter as well as supplement significantly increased serum selenium and SELENOP concentrations, while there were no changes in the placebo groups. Both interventions were equally effective in increasing selenium levels, but the upregulation of SELENOP was more pronounced in vegans than in omnivores. Conclusion: Brazil nuts are a plant-based source of selenium suitable for vegans and omnivores to improve their selenium status when consumed once in a while. Trial registration number and date of registration: Clinical trials registration number: NCT05814874, April 18 2023.
    Universitätsbibliographie Jena:
    fsu_mods_00020550Externer Link
  4. Standardizing Nutritional Care for Cancer Patients: Implementation and Evaluation of a Malnutrition Risk Screening

    ErscheinungsjahrErschienen in:Oncology research and treatment V. Mathies, A. Kipp, J. Hammersen, K. Schrenk, S. Scholl, U. Schnetzke, A. Hochhaus, T. Ernst
  5. Fostering healthy aging through selective nutrition: A long-term comparison of two dietary patterns and their holistic impact on mineral status in middle-aged individuals—A randomized controlled intervention trial in Germany

    ErscheinungsjahrErschienen in:Journal of Trace Elements in Medicine and Biology D. Pellowski, T. Heinze, M. Tuchtenhagen, S. Müller, S. Meyer, M. Maares, C. Gerbracht, C. Wernicke, H. Haase, A. Kipp, T. Grune, A. Pfeiffer, K. Mai, T. Schwerdtle
  6. Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum

    ErscheinungsjahrErschienen in:Metallomics: integrated biometal science S. Friese, G. Ranzini, M. Tuchtenhagen, K. Lossow, B. Hertel, G. Pohl, F. Ebert, J. Bornhorst, A. Kipp, T. Schwerdtle
    The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases. Here, the impact of long-term modulation of dietary intake of copper, iron, selenium, and zinc was investigated in murine cerebellum. Four- and 40-wk-old mice of both sexes were supplied with different amounts of those TEs for 26 wk. In an adequate supply group, TE concentrations were in accordance with recommendations for laboratory mice while suboptimally supplied animals received only limited amounts of copper, iron, selenium, and zinc. An additional age-adjusted group was fed selenium and zinc in amounts exceeding recommendations. Cerebellar TE concentrations were measured by inductively coupled plasma–tandem mass spectrometry. Furthermore, the expression of genes involved in TE transport, DNA damage response, and DNA repair as well as selected markers of genomic stability [8-oxoguanine, incision efficiency toward 8-oxoguanine, 5-hydroxyuracil, and apurinic/apyrimidinic sites and global DNA (hydroxy)methylation] were analysed. Ageing resulted in a mild increase of iron and copper concentrations in the cerebellum, which was most pronounced in the suboptimally supplied groups. Thus, TE changes in the cerebellum were predominantly driven by age and less by nutritional intervention. Interestingly, deviation from adequate TE supply resulted in higher manganese concentrations of female mice even though the manganese supply itself was not modulated. Parameters of genomic stability were neither affected by age, sex, nor diet. Overall, this study revealed that suboptimal dietary TE supply does not substantially affect TE homeostasis in the murine cerebellum.
    Universitätsbibliographie Jena:
    fsu_mods_00010730Externer Link
  7. Determination of copper status by five biomarkers in serum of healthy women

    ErscheinungsjahrErschienen in:Journal of Trace Elements in Medicine and Biology T. Chillon, M. Tuchtenhagen, M. Schwarz, J. Hackler, R. Heller, P. Kaghazian, A. Moghaddam, L. Schomburg, H. Haase, A. Kipp, T. Schwerdtle, M. Maares
    Background: The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. Objectives: The aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. Method and main findings: This observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. Conclusions: This study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.
    Universitätsbibliographie Jena:
    fsu_mods_00012199Externer Link
  8. Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells

    ErscheinungsjahrErschienen in:Redox Biology A. Thiel, F. Drews, M. Pirritano, F. Schumacher, V. Michaelis, M. Schwarz, S. Franzenburg, T. Schwerdtle, B. Michalke, A. Kipp, B. Kleuser, M. Simon, J. Bornhorst
    Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2). The results reveal a synergistic effect of Co and Ni, leading to significantly higher number of differentially expressed genes (DEGs) compared to individual exposure. There was a clear enrichment of Nrf2 regulated genes linked to pathways such as glycolysis, iron and glutathione metabolism, and sphingolipid metabolism, confirmed by targeted analysis. Co and Ni exposure alone and combined caused nuclear Nrf2 translocation, while only combined exposure significantly affects iron and glutathione metabolism, evidenced by upregulation of HMOX-1 and iron storage protein FTL. Both metals impact sphingolipid metabolism, increasing dihydroceramide levels and decreasing ceramides, sphingosine and lactosylceramides, along with diacylglycerol accumulation. By combining transcriptomics and analytical methods, this study provides valuable insights into molecular mechanisms of Co and Ni toxicity, paving the way for further understanding of metal stress.
    Universitätsbibliographie Jena:
    fsu_mods_00015681Externer Link
  9. Intrazelluläre Phospholipase A2 und Membranfettsäureprofile bei Hochrisikopatienten für psychotische Störungen und der metabolische Einfluss einer indizierten Prävention durch Omega-3-Fettsäuren

    Erscheinungsjahr V. Kersten
    Psychotische Störungen gehören zu den schwersten psychischen Erkrankungen. Im Rahmen der Psychosefrüherkennungs-Forschung wurden Kriterien zur Identifikation von Personen mit erhöhtem Psychoserisiko entwickelt und der Begriff ultra-high risk (UHR) geprägt. Durch ein frühestmögliches Eingreifen sollte der Übergang in die akute Manifestationsform (sog. Transition) verhindert, verzögert oder der klinische Verlauf verbessert werden. Als Ausgangspunkt für die indizierte Prävention diente im Rahmen der vorliegenden Arbeit die Membranphospholipid-Hypothese, welche von einem Defizit an mehrfach ungesättigten Fettsäuren sowie einer erhöhten Aktivität der intrazellulären Phospholipase A2 (inPLA2) ausgeht. Dem sollte durch eine Substitution von Omega-3-Fettsäuren (Omega-3-FS) im frühen Stadium der Ätiopathogenese entgegengewirkt werden. Ziel dieser Forschungsarbeit war es, als Teilaspekt der multizentrischen, prospektiv-randomisierten Interventionsstudie NEURAPRO (McGorry et al. 2017) in der UHR-Population die inPLA2-Aktivität und deren Assoziation zum Fettsäureprofil zu untersuchen sowie der prädiktiven Aussagekraft der inPLA2-Aktivität in Bezug auf die Transition nachzugehen. Die Stichprobe umfasste 138 UHR-Patient:innen der Interventions- (Omega-3-FS) und 126 UHR-Patient:innen der Placebo-Gruppe. Die Bestimmung der inPLA2-Aktivität erfolgte fluorometrisch im Blutserum unter Verwendung des PLA2-Substrates PED6 zu Studienbeginn (Baseline, M0) und nach der sechswöchigen Intervention (Follow-up, M6). Zu Baseline zeigte sich eine inverse Korrelation zwischen der inPLA2-Aktivität und der Membranverfügbarkeit an Omega-3-FS. In den Verlaufsanalysen konnte ungeachtet der Interventionsbedingung ein Anstieg der inPLA2-Aktivität bei Transition-Patient:innen sowie eine damit einhergehend höhere inPLA2-Aktivität als bei Non-Transition-Patient:innen bei M6 verzeichnet werden. Dies deutet auf eine zeitliche Dynamik der inPLA2-Aktivität im unmittelbaren Vorfeld der Transition hin.
    Universitätsbibliographie Jena:
    fsu_mods_00015436Externer Link
  10. Charakterisierung der Auswirkungen von Tylosin und Chlorotonil auf die Phylogenie und Funktionalität des intestinalen Mikrobioms junger Schweine durch Meta-Omics-Analysen

    Erscheinungsjahr S. Wagner
    Universitätsbibliographie Jena:
    fsu_mods_00014912Externer Link
  11. NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium

    ErscheinungsjahrErschienen in:Antioxidants: open access journal A. Löser, M. Schwarz, A. Kipp
    Background: Selenium and zinc are essential trace elements known to regulate cellular processes including redox homeostasis. During inflammation, circulating selenium and zinc concentrations are reduced in parallel, but underlying mechanisms are unknown. Accordingly, we modulated the zinc and selenium supply of HepG2 cells to study their relationship. Methods: HepG2 cells were supplied with selenite in combination with a short- or long-term zinc treatment to investigate intracellular concentrations of selenium and zinc together with biomarkers describing their status. In addition, the activation of the redox-sensitive transcription factor NRF2 was analyzed. Results: Zinc not only increased the nuclear translocation of NRF2 after 2 to 6 h but also enhanced the intracellular selenium content after 72 h, when the cells were exposed to both trace elements. In parallel, the activity and expression of the selenoprotein thioredoxin reductase 1 (TXNRD1) increased, while the gene expression of other selenoproteins remained unaffected or was even downregulated. The zinc effects on the selenium concentration and TXNRD activity were reduced in cells with stable NRF2 knockdown in comparison to control cells. Conclusions: This indicates a functional role of NRF2 in mediating the zinc/selenium crosstalk and provides an explanation for the observed unidirectional behavior of selenium and zinc.
    Universitätsbibliographie Jena:
    fsu_mods_00017936Externer Link
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