Forschung / Research

Übersicht zu Forschungsarbeiten

Bild von Immunfluoreszenzmikroskop

Foto: Maria Schwarz
Bild von Immunfluoreszenzmikroskop

ORCID: http://orcid.org/0000-0002-3307-1038Externer Link

Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/?term=anna+kippExterner Link

ResearchGate: https://www.researchgate.net/profile/Anna_KippExterner Link

Current Research Projects

Nature 4 health (Thüringer Aufbaubank, 2024-2027)

In this research unit we aim to evaluate selected natural products, natural product extracts, and physiologically relevant nutrients for the treatment of chronic inflammation and to elucidate their mechanisms of action and efficacy. By combining these promising natural compounds with selenium, vitamin E, or omega-3 fatty acids, the aim is to achieve synergistic improvements in their properties. The Free State of Thuringia is funding the group for three years using resources from the European Social Fund Plus (ESF Plus). We focussed on the DSS-indiced colitis model as well as MASLD induced by high fat/high fructose diets with parallel modulation of selenium and or copper.

Nature 4 health Homepage: https://www.bce.uni-jena.de/297/nature4health

Key publications:

Lossow K, Maares M, Heinze T, Pellowski D, Richter E, Schröder K, Dahmen L, Schüßler C, Renko K, Schwerdtle T, Haase H, Kipp AP (2026). Distribution interactions of the trace elements zinc, copper, and selenium under conditions of their parallel deficiency, Redox Biol. 89:103963. doi: 10.1016/j.redox.2025.103963Externer Link.

Further publications are in preparation.

Identification and manipulation of the psychosomatic clocks across the lifespan (IMPULS) (Carl-Zeiss-Stiftung, 2021-2027)

Samples obtained through the "Aging as Future" (Altern als Zukunft) study will be utilized. The project aims to assess the status of trace elements such as copper, selenium, iron, and zinc by analyzing both concentration levels and functional biomarkers. Furthermore, changes in macronutrient intake will be investigated by examining serum levels of fatty acids and amino acids. This analysis will determine whether the measured biological parameters offer a meaningful complement to existing clocks. Subsequently, the insights gained will be used to study the impact of nutritional interventions on aging parameters and lifespan clocks in model organisms.

IMPULS-Homepage: https://www.impuls.uni-jena.de/de/24/forschung

Key publications:

Herpich C, Heinze T, Moskiou V, Kalymon M, Göger L, Faust L, Lossow K, Müller-Werdan U, Schwerdtle T, Schomburg L, Kipp AP, Norman K (2026). Three-dimensional trace element profile reflecting aging, disease, and frailty. Geroscience. doi: 10.1007/s11357-026-02181-3.Externer Link

Eroglu B, Eichelmann F, Doerre J, Kuxhaus O, Kipp AP, Schwerdtle T, Schomburg L, Schulze MB (2026). Serum trace element levels and their associations with handgrip strength: a cross-sectional study among non-diabetic older adults in Germany. Geroscience. doi: 10.1007/s11357-026-02147-5Externer Link.

Prada M, Bezuhla O, Kuxhaus O, Eichelmann F, Jäger S, Kipp AP, Haase H, Schwerdtle T, Schulze MB (2025). Interaction of serum zinc and copper status with fatty acid desaturases on incidence of type 2 diabetes in the EPIC-Potsdam study. Redox Biol.; 90:103998. doi: 10.1016/j.redox.2025.103998Externer Link.

Meyer CE, Vukelic N, Mariadason JM, Kipp AP (2025). Connecting concentrations of copper, selenium, and zinc with transcriptomic and proteomic data of well-characterized human colorectal cancer cell lines. J Trace Elem Med Biol.;89:127638. doi: 10.1016/j.jtemb.2025.127638Externer Link.

Schwarz M, Kipp AP (2024). PRDX6 as an additional piece in the puzzle of selenoprotein synthesis. Mol Cell.;84(23):4475-4477. doi: 10.1016/j.molcel.2024.11.010.Externer Link

Löser A, Schwarz M, Kipp AP (2024). NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium, Antioxidants. 13:1211. doi: 10.3390/antiox13101211.Externer Link

Karolinska Project (2020-2027)

Trace elements such as copper, zinc, and selenium are essential nutrients for humans. In addition to nutrient intake and bioavailability, there appear to be individual differences in the homeostatic regulation of trace elements which are influenced by factors such as sex, age, physical activity, and stress that have not yet been systematically investigated. Accordingly, our goal is to characterize in greater detail the interplay between these factors and the homeostatic regulation of trace elements. In addition, we analyse the role of trace elements in cancer.

 

Key publications:

Simon R, Röhr W, Schwarz M, Haase H, Puta C, Kipp AP (2026). Acute effects of physical exercise on biomarkers of the trace elements selenium, zinc, copper, and iron. J Trace Elem Med Biol.;94:127828. doi: 10.1016/j.jtemb.2026.127828Externer Link.

Simon R, Lossow K, Pellowski D, Kipp K, Achatz M, Klasen N, Schwerdtle T, Dawczynski C, Kipp AP (2025). Improving the selenium supply of vegans and omnivores with Brazil nut butter compared to a dietary supplement in a randomized controlled trial. Eur J Nutr.; 64(2):74. doi: 10.1007/s00394-025-03587-zExterner Link.

Meyer CE, Schwarz M, Meyer FB, Thierbach R, Kipp AP (2025). Supranutritional Selenomethionine but not Selenite Reduces Malignant Cell Transformation. Biol Trace Elem Res. 2025 Jun 25. doi: 10.1007/s12011-025-04719-6Externer Link.

Simon R, Lossow K, Pellowski D, Kipp K, Achatz M, Klasen N, Schwerdtle T, Dawczynski C, Kipp AP (2025). Improving the selenium supply of vegans and omnivores with Brazil nut butter com-pared to a dietary supplement in a randomized controlled trial, Eur. J. Nutr. 64:74. doi: 10.1007/s00394-025-03587-zExterner Link.

Schwarz M, Löser A, Cheng Q, Wichmann-Costaganna M, Schädel P, Werz O, Arnér ES, Kipp AP (2023). Side-by-side comparison of recombinant human glutathione peroxidases identifies over-lapping substrate specificities for soluble hydroperoxides, Redox Biol., 59:102593. doi: 10.1016/j.redox.2022.102593Externer Link

Klein L, Dawczynski C, Schwarz M, Maares M, Kipp K, Haase H, Kipp AP (2023). Selenium, Zinc, and Copper Status of Vegetarians and Vegans in Comparison to Omnivores in the Nutritional Evaluation (NuEva) Study, Nutrients. 15(16):3538. doi: 10.3390/nu15163538Externer Link.

Completed Externally Funded Research Projects

1. DFG Research Unit on Interactions of essential trace elements in healthy and diseased elderly (TraceAge, 2017-2024)

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

Logo TraceAge

Logo TraceAge

Foto: TraceAge

In TraceAge, we demonstrated that low dietary supply of the trace elements Cu, Fe, I, Mn, Se, and Zn in mice led to growth retardation and an increased spleen weight compared with mice receiving adequate trace element intake, highlighting the high sensitivity of the immune system to changes in trace element supply. We also identified Nrf2 as an important regulator of trace element homeostasis and interrelated trace element pathways. Moreover, murine age-related trace element profiles proved to be highly stable and could not be altered by age-adapted diets designed to adjust trace element intake according to age-dependent changes in serum concentrations. Finally, we identified a novel interaction between selenium and copper, showing that elevated hepatic copper levels impair the release of SELENOP.

Key publications:

Lossow K, Maares M, Heinze T, Pellowski D, Richter E, Schröder K, Dahmen L, Schüßler C, Renko K, Schwerdtle T, Haase H, Kipp AP (2026). Distribution interactions of the trace elements zinc, copper, and selenium under conditions of their parallel deficiency, Redox Biol. 89:103963. doi: 10.1016/j.redox.2025.103963Externer Link.

Herpich C, Heinze T, Moskiou V, Kalymon M, Göger L, Faust L, Lossow K, Müller-Werdan U, Schwerdtle T, Schomburg L, Kipp AP, Norman K (2026). Three-dimensional trace element profile reflecting aging, disease, and frailty. Geroscience. doi: 10.1007/s11357-026-02181-3Externer Link.

Schwarz M, Meyer CE, Löser A, Lossow K, Hackler J, Ott C, Jäger S, Mohr I, Eklund EA, Patel AAH, Gul N, Alvarez S, Altinonder I, Wiel C, Maares M, Haase H, Härtlova A, Grune T, Schulze MB, Schwerdtle T, Merle U, Zischka H, Sayin VI, Schomburg L, Kipp AP (2023). Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P, Nat. Commun. 14(1):3479. doi: 10.1038/s41467-023-39245-3.Externer Link

Lossow K, Renko K, Schwarz M, Schomburg L, Schwerdtle T*, Kipp AP* (2021). The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice, Nutri-ents, 13:3773. doi: 10.3390/nu13113773Externer Link.

Wandt VK, Winkelbeiner N, Lossow K, Kopp JF, Schwarz M, Alker W, Nicolai M, Simon L, Dietzele C, Zimmermann S, Hertel B, Pohl G, Ebert F, Schomburg L, Haase H, Bornhorst J, Kipp AP*, Schwerdtle T* (2021). Aging-associated effects of a long-term dietary modulation of four trace elements in mice, Redox Biol., 46:102083. doi: 10.1016/j.redox.2021.102083Externer 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

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

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 

2. Functions of GPX2 in the healthy intestine, during inflammatory processes, and colorectal carcinogenesis (DFG 2012-2015)

In a model of inflammation-induced colorectal carcinogenesis, we demonstrated that glutathione peroxidase 2 (GPX2) exerts an anti-inflammatory effect and thereby reduces tumor growth. In contrast, GPX2 promoted tumor development in a model of sporadic colon cancer. The present project aimed to elucidate the molecular mechanisms underlying these opposing effects. Additionally, other, hitherto less characterized selenoproteins such as SELENOH were to be investigated.

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 (PhD/PostDoc project)

We investigated 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.  We provided insights into molecular effects such as modulated signaling pathways, metabolite profiles, and epigenetic regulators influenced by suboptimal selenium supply.

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

57 Publikationen filtern

Die Publikationen filtern

Hervorgehobene Autoren sind Mitglieder der Forschungsgruppe.

  1. Interaction of serum zinc and copper status with fatty acid desaturases on incidence of type 2 diabetes in the EPIC-Potsdam study

    Autoren M. Prada, O. Bezuhla, O. Kuxhaus, F. Eichelmann, S. Jäger, A. Kipp, H. Haase, T. Schwerdtle, M. Schulze ErscheinungsjahrErschienen in:Redox Biology
    Aims: To examine whether zinc (Zn) and copper (Cu) status influence the association of estimated delta-5 desaturase (D5D), delta-6 desaturase (D6D), and stearoyl-CoA desaturase-1 (SCD1) activities with type 2 diabetes (T2D) risk. Methods: We used a nested case-cohort design within the EPIC–Potsdam Study (n = 1979; 447 incident T2D cases). Desaturase activities were estimated using erythrocyte fatty acids (FA): D5D (20:4n-6/20:3n-6), D6D (18:3n-6/18:2n-6), and SCD1 (16:1/16:0 [SCD1-16], 18:1/18:0 [SCD1-18]). We evaluated associations between desaturases and serum Zn or Cu, assessed interactions between serum Zn or Cu and desaturase activities in Cox regression models for T2D risk, and examined modification by Zn transporter SLC30A8 genetic variant and metal-related polygenic risk scores. Results: Higher serum Zn was significantly associated with lower SCD1-18 activity (β per 1 SD = −0.09). Zn status showed a non-linear modifying effect on the D5D-T2D relationship (p-interaction = 0.03), though an inverse D5D association was observable consistently across Zn levels. Serum Cu was positively associated with SCD1-16 (β = 0.13) and SCD1-18 (β = 0.08) and negatively associated with D5D activity (β = −0.13). Stronger inverse associations of higher D5D activity with T2D risk were observed at low Cu levels (HR 0.69, 95% CI 0.58–0.81) versus higher levels (HR 0.95, 95% CI 0.80–1.13) (p-interaction = 0.009). The SLC30A8 variant rs13266634 significantly modified the D5D-T2D association. Furthermore, the inverse association of D5D with T2D was stronger among participants with a higher Cu genetic score. Conclusions: Zn and Cu status modified the relationship between FA desaturases and T2D risk. This was supported by serum Zn and Cu levels and by genetic variation related to their transport and homeostasis.
    Universitätsbibliographie Jena:
    fsu_mods_00029845Externer Link

  2. Weighing the Benefits of Improving the Iron Status Against the Risk of Overload—A Narrative Review on Oral Iron Supplementation in Premenopausal Women

    Autoren K. Jans, P. Huebbe, A. Kipp, G. Rimbach ErscheinungsjahrErschienen in:Biofactors
    To this day, women of childbearing age remain the largest group at high risk for iron deficiency worldwide. This global health issue impairs quality of life and, if not adequately managed, can lead to serious health consequences. Menstruating women face high iron requirements that are often challenging to meet through diet alone. Consequently, oral iron supplements offer a convenient, low-cost, widely available, and commonly employed strategy to approach iron deficiency. Iron plays a key role in many essential body functions. However, due to its corrosive nature and cytotoxic properties, strict homeostasis is crucial, and oral interventions warrant careful consideration. This narrative review examines the benefits and potential drawbacks of oral iron supplements as a frontline approach to addressing the most prevalent nutrient deficiency in menstruating females from a nutritionist's perspective.
    Universitätsbibliographie Jena:
    fsu_mods_00036467Externer Link

  3. Serum trace element levels and their associations with handgrip strength: a cross-sectional study among non-diabetic older adults in Germany

    Autoren B. Eroglu, F. Eichelmann, J. Doerre, O. Kuxhaus, A. Kipp, T. Schwerdtle, L. Schomburg, M. Schulze ErscheinungsjahrErschienen in:GeroScience: dedicated to the biomedical investigation of geroscience and the basic mechanisms of aging
    Background: Handgrip strength is an important marker of health status and is influenced by modifiable risk factors, including dietary intake. Trace elements (TE) copper, iron, iodine, manganese, selenium, and zinc are involved in physiological processes relevant to muscle function. However, the individual and interactive effects of these TE on handgrip strength have not been investigated in community-dwelling non-diabetic older adults. We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising 1432 participants (median age 67 years, 59% female). Serum TE levels were measured using inductively coupled plasma tandem mass spectrometry, and handgrip strength was measured using a dynamometer. Associations between TE and handgrip strength were investigated with multivariable regression models. Interactions and non-linear effects were assessed using Bayesian Kernel Machine Regression (BKMR). Higher serum manganese levels were inversely associated with handgrip strength in multivariable linear regression models (β −0.011, 95% CI −0.019; −0.003). In logistic regression analyses, higher serum manganese levels were associated with higher odds of having low strength (OR per SD 1.25, 95% CI 1.10–1.48), and higher serum selenium levels were associated with lower odds of having low strength (0.83, 0.70–0.97). We did not observe any association between other TE and handgrip strength. BKMR analyses did not indicate strong interactive effects of TE on handgrip strength. Our findings indicate that higher serum manganese levels are associated with lower handgrip strength, and lower serum selenium levels are associated with higher odds of having low strength among community-dwelling non-diabetic older adults.
    Universitätsbibliographie Jena:
    fsu_mods_00035177Externer Link

  4. Vitamin A acts as a potent suppressor of selenoprotein P with potential relevance for multivitamin supplementation

    Autoren S. Karmeli, T. Chillon, R. Sane, M. Schwarz, U. Gröber, J. Hackler, A. Kipp, L. Schomburg ErscheinungsjahrErschienen in:The journal of nutritional biochemistry
    Multivitamin supplementation is a widely used strategy to prevent disease, slow the ageing process, improve quality of life and extend life span, although recent clinical findings do not support these claims. Since selenium (Se) deficiency is associated with morbidity and mortality risk, we tested the hypothesis that certain vitamins interfere with the regular biosynthesis of the Se transporter selenoprotein P (SELENOP). Human liver cancer cells (HepG2) were treated with different concentrations of folic acid, nicotinamide, nicotinic acid, pyridoxal phosphate, thiamine, vitamin A, vitamin C, vitamin D2, vitamin D3, vitamin E, vitamin K and vitamin B12. Secreted SELENOP was quantified by ELISA and characterized by Western blot analysis. SELENOP transcript levels and promoter activity were determined, and resveratrol as a negative and thyroid hormone as a positive modulator were included for comparison. The concentration of extracellular SELENOP decreased twofold in response to micromolar concentrations of vitamin A. The SELENOP transcript concentration decreased to 70% after incubation with 1 µM vitamin A, and a moderate concomitant decrease in SELENOP core promoter activity was observed. Co-incubation experiments of vitamin A with the active thyroid hormone T3 revealed dose-dependent effects and suggested competitive activities of these two modifiers of SELENOP expression in opposite directions. We conclude that vitamin A is able to suppress hepatic SELENOP biosynthesis and secretion, which may confer health risks in self-administered or clinically indicated supplementation with retinoids, especially in individuals with marginal Se intake and status.
    Universitätsbibliographie Jena:
    fsu_mods_00028865Externer Link

  5. Three-dimensional trace element profile reflecting aging, disease, and frailty

    Autoren C. Herpich, T. Heinze, V. Moskiou, M. Kalymon, L. Göger, L. Faust, K. Lossow, U. Müller-Werdan, T. Schwerdtle, L. Schomburg, A. Kipp, K. Norman ErscheinungsjahrErschienen in:GeroScience: dedicated to the biomedical investigation of geroscience and the basic mechanisms of aging
    Older age combined with chronic disease increases the risk of malnutrition and frailty, impacting disease recovery and overall clinical outcomes. Serum concentrations of several trace elements and their respective biomarkers have not yet been investigated with regard to frailty in older adults with disease, although these patients most likely have an altered trace element profile owing to both inflammatory conditions and inadequate dietary intake. This cross-sectional study investigated trace element profiles in relation to age, disease, and frailty status in geriatric patients (n = 198) as well as in old (n = 80) and young (n = 60) healthy controls. Serum concentrations of iron, zinc, selenium, iodine, copper, and manganese were quantified via ICP-MS/MS, alongside inflammatory markers and functional biomarkers. Analysis revealed distinct trace element profiles in patients compared to healthy controls, with lower manganese, iron, zinc, and selenium, but higher copper and iodine (p ≤ 0.001). Trace element concentrations were similar in young and older healthy controls. Principal component (PC) analysis identified two profiles. PC1 was negatively associated with age, number of drugs, sex, and inflammation. Only PC2 was associated with anorexia (β = 0.053 ± 0.020; 95% CI 0.015, 0.092; p = 0.007). Furthermore, intake of drugs that affect intestinal trace element absorption was associated with PC2. Our analyses suggest that PC1 might reflect disease/inflammation, and PC2 inadequate trace element supply. These cross-sectional findings suggest that inflammation and inadequate trace element intake, rather than age, significantly influence trace element profiles and contribute to frailty. Trail registration number: DRKS00017090, registered 12.04.2019; DRKS00028105, registered 03.03.2022.
    Universitätsbibliographie Jena:
    fsu_mods_00035454Externer Link

  6. Interactions of copper and selenium and their role in cancer

    Autor C. Meyer Erscheinungsjahr
    Selenium and copper are essential trace elements with diverse functions for human health. Selenium’s biological functions are mainly attributed to selenoproteins. Copper acts as a structural component, enzymatic cofactor, or metalloallosteric regulator of proteins. Both trace elements are metabolized in the liver, where the selenium-transporting protein SELENOP is synthesized and where copper can interfere with selenium metabolism. In addition, there might be a potential interaction between copper and selenium and dysregulated metabolisms during cancer, since both trace elements seem to accumulate in tumor tissue. Moreover, copper-related proteins and selenoproteins showed a differential expression in tumor cells compared to healthy cells. Several tumor-promoting mechanisms have been described for copper. In contrast, an adequate supply with selenium is supposed to prevent tumor initiation by a concomitant optimized selenoprotein activity. The overall aim of this dissertation was to investigate the interaction between copper and selenium and the role of a modulated supply with copper and selenium in carcinogenesis. This dissertation confirmed an interaction between elevated hepatic copper and selenium metabolism by revealing a copper-induced hepatic SELENOP accumulation and a concomitant decreased systemic selenium status. This might be of special importance for individuals with a prior suboptimal selenium supply and potentially for cancer patients. While results support a tumor-promotive role of copper, physiologically relevant modulated selenium supply was not associated with altered malignant cell transformation. Only supranutritional selenomethionine but not selenite reduced the malignant cell transformation, most probably via mechanisms independent of optimizing selenoprotein synthesis and activity, revealing selenium-species dependent effects. Hence, chemopreventive effects of selenium and the regulation of selenoproteins may be unrelated phenomena.
    Universitätsbibliographie Jena:
    fsu_mods_00036886Externer Link

  7. Distribution interactions of the trace elements zinc, copper, and selenium under conditions of their parallel deficiency

    Autoren K. Lossow, M. Maares, T. Heinze, D. Pellowski, E. Richter, K. Schröder, L. Dahmen, C. Schüßler, K. Renko, T. Schwerdtle, H. Haase, A. Kipp ErscheinungsjahrErschienen in:Redox Biology
    Trace elements such as copper, zinc, and selenium are essential micronutrients that play crucial roles in various physiological processes, mainly through their involvement in enzymes and regulatory proteins. A deficiency of any of these elements can impair physiological functions and lead to a range of symptoms. While copper deficiency is rare, e.g., vegans are particularly susceptible to inadequate intake of zinc and selenium. To investigate the effects of multiple simultaneous deficiencies, a feeding study was conducted in adult male and female C57BL/6Jrj mice receiving diets low in copper, zinc, and selenium. This approach enabled us to explore potential interactions between trace elements and to identify organ-specific effects based on their distribution profiles. We observed a substantial depletion of copper and selenium concentrations in the circulation and in almost all organs although to a varying extent. In contrast, zinc levels were well maintained and only declined in serum and bone. In line with the well-known antagonistic relationship between copper and zinc, our findings revealed that zinc deficiency mitigated symptoms of copper deficiency, which was most pronounced in female mice. Moreover, copper deficiency led to increased selenium concentrations in various organs, which, however, was not accompanied by generally higher selenoprotein expression. Therefore, it is essential to consider potential effects of single trace element deficiencies on other trace elements taking also combined effects into account.
    Universitätsbibliographie Jena:
    fsu_mods_00029534Externer Link

  9. Acute effects of physical exercise on biomarkers of the trace elements selenium, zinc, copper, and iron

    Autoren R. Simon, W. Röhr, M. Schwarz, H. Haase, C. Puta, A. Kipp ErscheinungsjahrErschienen in:Journal of Trace Elements in Medicine and Biology
    Background Physical activity is important for a healthy lifestyle but may have side effects, especially when performed in an excessive manner. This includes effects on the immune system but can also result in a higher need for certain micronutrients such as the trace elements selenium, zinc, copper, and iron. Objective This study aimed to characterize short-term effects of a standardized 1-minute sit-to-stand-test (STST) on serum concentrations of these trace elements. Methods 20 healthy individuals performed the STST. Capillary blood samples were drawn 10 min before, immediately after, 30, and 60 min post-exercise. Lactate, glucose, and blood cell counts were determined together with the systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI) and neutrophil-to-lymphocyte ratio (NLR). The trace element concentrations and the biomarkers free zinc (fZn), and selenoprotein P (SELENOP) were analysed. All values except for fZn and NLR were adjusted for hemoconcentration. Results Immediately after the STST, the levels of copper and selenium decreased significantly, which subsequently returned to baseline values. SELENOP levels showed a similar pattern to that of total selenium concentrations but only increased significantly after 60 min, compared to immediately after exercise. In contrast, no changes were observed for total zinc concentrations. FZn increased significantly immediately after the STST, before decreasing. Iron levels were higher immediately after the STST and rose significantly after 60 min. The cellular inflammatory markers NLR and SII decreased significantly after exercise and then increased compared to pre-test values. However, this was only significant for NLR. In contrast, SIRI increased continuously after physical activity, reaching significantly higher values after 60 min. Conclusion Short-term acute physical exercise modulates serum trace element concentrations together with inflammatory parameters. Accordingly, these might be connected to each other which should be analyzed after more extensive, long-term or repeated exercise.
    Universitätsbibliographie Jena:
    fsu_mods_00030227Externer Link

  10. Evolutionary Conservation of the Copper-Dependent Thiol Oxidase Activity of Selenium-Binding Proteins

    Autoren H. Schlemminger, S. Lockowandt, A. Löser, A. Kipp, L. Klotz, H. Steinbrenner ErscheinungsjahrErschienen in:Antioxidants: open access journal
    Human selenium-binding protein 1 (SELENBP1) is a methanethiol oxidase (MTO), converting methanethiol (MT) to hydrogen sulfide (H ₂ S), hydrogen peroxide (H ₂ O ₂ ) and formaldehyde (HCHO). SELENBP1 has orthologs in all domains of life. RdMTO, an orthologous enzyme recently identified in the marine bacterium Roseobacter denitrificans, was postulated to require the cysteine residue closest to its C-terminus, Cys448, for MT binding and to oxidize MT to sulfane sulfur (S ⁰ ) rather than to H ₂ S. SELENBP1 and RdMTO exhibit ~53% sequence identity, with Cys448 (numbered Cys466 in SELENBP1) and amino acids required for copper binding being conserved. Therefore, we here compared the MTO activity of recombinant SELENBP1 and RdMTO. We found that SELENBP1, like RdMTO, converts MT as well as structurally related alkyl thiols to form H ₂ S, H ₂ O ₂ and, in the case of MT, HCHO in a strictly copper-dependent manner. MTO activity of both proteins was lowered but not abrogated upon mutation of their respective C-terminal cysteine residue. Thus, the catalytic mechanism of selenium-binding proteins that act as copper-dependent MTOs appears to be evolutionarily conserved from bacteria to humans. Presumably, this enzyme is an early evolutionary invention of prokaryotes, in order to cope with toxic thiols in their environment.
    Universitätsbibliographie Jena:
    fsu_mods_00044010Externer Link

  11. Alternatives to animal models in gastroenterology and hepatology research

    Autoren E. Gardey, A. Geisler, A. Löser, A. Stallmach, A. Kipp, S. Lorkowski, M. Witt-Wallert ErscheinungsjahrErschienen in:Frontiers in Pharmacology
    The accurate definition of in vivo, ex vivo and in vitro models is critical for the whole R&D process, i.e., basic research, clinical translation and reliability of results. Although many models are currently being developed, it is important to recognize the limitations and advantages of each of them. The aim of this review is to compile the most important alternatives to animal models in the fields of gastroenterology and hepatology research. A thorough comparison and understanding of each alternative model will certainly save time and money and will lead to better predictability and reliability of results for clinical translation and clinical trials. There is no single model capable of replacing the complexity of human biology. Nevertheless, it is essential to understand the fundamentals of human anatomy, physiology and disease pathophysiology to select the most appropriate model in translational research. At the same time, the appropriate model must be selected to gain a deeper understanding of the principal processes underlying human physiology and the pathology of diseases.
    Universitätsbibliographie Jena:
    fsu_mods_00036205Externer Link

  12. Hepatic methanethiol oxidase (MTO) activity of mice requires adequate dietary supply of copper

    Autoren N. Krafczyk, K. Lossow, L. Biegel, N. Meinhardt, M. Schwarz, H. Zischka, H. Steinbrenner, A. Kipp, L. Klotz ErscheinungsjahrErschienen in:Redox Biology
    Selenium-binding protein 1 (SELENBP1) catalyzes the oxidative conversion of methanethiol to hydrogen sulfide, hydrogen peroxide and formaldehyde. Methanethiol oxidase (MTO) activity of recombinant human SELENBP1 was shown to require copper (Cu) ions, whereas selenium (Se) was largely dispensable. However, the impact of Cu and Se on MTO activity in mammals has not been explored so far. To investigate whether SELENBP1 levels and MTO activity in mice are affected by dietary availability of trace elements, liver samples of C57BL/6JRj mice held on diets deficient in Cu and/or Se for eight weeks were analyzed, as compared to mice fed the control diet with adequate trace element supply. Dietary Cu deficiency always resulted in diminished hepatic MTO activity, as detected by methanethiol-derived production of hydrogen sulfide. The effect of Cu deficiency was more pronounced in male than in female mice. Se deficiency only slightly, and solely in males, lowered MTO activity. Another sex-specific effect was observed with hepatic SELENBP1 levels: whereas diets deficient in Cu and/or Se increased SELENBP1 levels in males, they were decreased in female mice under Cu-deficient conditions. In addition to dietary Cu deficiency, MTO activity and SELENBP1 levels were explored in a rat model of Wilson's disease, which is characterized by hepatic Cu accumulation. Hepatic MTO activity was not altered in male and female rats under conditions of excess intrahepatic Cu, as long as the liver was not severely damaged. Notwithstanding the relatively low number of 5-6 animals included in each group, our data allow for the conclusion that hepatic MTO activity depends on adequate dietary Cu supply, whereas excess Cu does not further enhance the MTO activity of SELENBP1.
    Universitätsbibliographie Jena:
    fsu_mods_00039798Externer Link
Paginierung Seite 1