Plant-based diets usually contain more nutrient-dense foods such as vegetables, legumes, whole gr... more Plant-based diets usually contain more nutrient-dense foods such as vegetables, legumes, whole grains, and fruits than a standard Western diet. Yet, the amount and especially the bioavailability of several nutrients, such as trace elements, is supposed to be lower in comparison to diets with consumption of animal-derived foods. Based on this, the Nutritional Evaluation (NuEva) study (172 participants) was initiated to compare the trace element status of omnivores, flexitarians, vegetarians, and vegans. Serum selenium, zinc, and copper concentrations and biomarkers were evaluated at baseline and during a 12-month intervention with energy- and nutrient-optimized menu plans. The implementation of optimized menu plans did not substantially influence the status of trace elements. At baseline, serum selenium biomarkers were lower in vegetarians and vegans compared to omnivores and flexitarians. The zinc intake of vegetarians and vegans was significantly lower compared to omnivores, wherea...
Eine optimale Versorgung mit den essentiellen Spurenelementen Selen, Kupfer, Zink, Eisen ist wich... more Eine optimale Versorgung mit den essentiellen Spurenelementen Selen, Kupfer, Zink, Eisen ist wichtig, da sowohl eine Spurenelementdefizienz als auch eine überdosierung schwerwiegende gesundheitliche Folgen haben kann. Bereits bei der Aufnahme der Spurenelemente im Dünndarm sind gemeinsame Transportmechanismen bekannt. Weiterhin sind die vier Spurenelemente Bestandteil vieler antioxidativer Enzyme, können jedoch in hohen Konzentrationen oxidativen Stress induzieren. Alle vier Spurenelemente sind an der zellulären Redoxhomöostase beteiligt, an deren Regulation der redox-sensitive Transkriptionsfaktor Nrf2 mitwirkt. Um ein besseres Verständnis zu den Interaktionen der vier Spurenelemente untereinander und mit der Redoxhomöostase zu erlangen, wurden verschiedene Fütterungsstudien an Mäusen durchgeführt, der Einfluss eines systemischen Nrf2-KOs auf die Spurenelementhomöostase untersucht und einzelne Kombinationen der Spurenelemente in vitro analysiert. Es konnte gezeigt werden, dass alle...
Postprints der Universität Potsdam: Mathematisch-Naturwissenschaftliche Reihe, Dec 1, 2020
Investigation of processes that contribute to the maintenance of genomic stability is one crucial... more Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA da...
Selenium and iodine are among the essential trace elements. Ensuring a comprehensive, adequate su... more Selenium and iodine are among the essential trace elements. Ensuring a comprehensive, adequate supply of these elements remains a challenge across the globe to this day, despite extensive efforts (such as the iodination of table salt). Factors that play a decisive role in the supply of these nutrients include not only soil conditions and traditional foods, but also the increasing spread of dietary trends, particularly in Europe. A recently published study recorded the nutrient intakes of 32,423 study participants (EPIC-Oxford cohort) using diet questionnaires adapted to the participants’ eating habits [1]. Both, this study and similar studies conducted in Germany showed that vegetarians had a lower selenium intake than people who consume meat and fish. Vegans are particularly at risk of inadequate iodine intake (exception: those who consume seaweed) [2]. The same conclusion was drawn by studies that used biomarkers to determine the status of both of these trace elements [3, 4]. In a...
Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones bu... more Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention. Markers of the selenium status were unaffected by the iodine supply. The thyroid gland was able to maintain serum thyroxine levels even under selenium-deficient conditions, despite reduced selenoprotein expression in liver and kidney, including deiodinase type 1. Thyroid hormone target genes responded to the altered selenium and iodine supply, whereas the iron, zinc, and copper homeostasis remained unaffected. There was a notable inte...
Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping... more Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences the expression of the selenoproteome in concert with the Se supply remains obscure. THP-1 monocytes were differentiated with phorbol 12-myristate 13-acetate (PMA) into macrophages and (i) the expression of selenoproteins, (ii) differentiation markers, (iii) the activity of NF-κB and NRF2, as well as (iv) lipid mediator profiles were analyzed. Se and differentiation affected the expression of selenoproteins in a heterogeneous manner. GPX4 expression was substantially decreased during differentiation, whereas GPX1 was not affected. Moreover, Se increased the expression of selenoproteins H and F, which was further enhanced by differentiation for selenoprotein F and diminished for selenoprotein H. Notably, LPS-induced expression of NF-κB target genes was facilitated...
Purpose We aimed to examine the prospective association between manganese, iron, copper, zinc, io... more Purpose We aimed to examine the prospective association between manganese, iron, copper, zinc, iodine, selenium, selenoprotein P, free zinc, and their interplay, with incident type 2 diabetes (T2D), cardiovascular disease (CVD) and colorectal cancer (CRC). Methods Serum trace element (TE) concentrations were measured in a case-cohort study embedded within the EPIC-Potsdam cohort, consisting of a random sub-cohort (n = 2500) and incident cases of T2D (n = 705), CVD (n = 414), and CRC (n = 219). TE patterns were investigated using principal component analysis. Cox proportional hazard models were fitted to examine the association between TEs with T2D, CVD and CRC incidence. Results Higher manganese, zinc, iodine and selenium were associated with an increased risk of developing T2D (HR Q5 vs Q1: 1.56, 1.09–2.22; HR per SD, 95% CI 1.18, 1.05–1.33; 1.09, 1.01–1.17; 1.19, 1.06–1.34, respectively). Regarding CVD, manganese, copper and copper-to-zinc ratio were associated with an increased r...
N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capabili... more N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capability. However, to date it is not well characterized whether NAC intake affects the homeostasis of essential trace elements. As a precursor of glutathione (GSH), NAC also has the potential to modulate the cellular redox homeostasis. Thus, we aimed to analyze effects of acute and chronic NAC treatment on the homeostasis of copper (Cu) and zinc (Zn) and on the activity of the redox-sensitive transcription factor Nrf2. Cells were exposed to 1 mM NAC and were co-treated with 50 μM Cu or Zn. We showed that NAC treatment reduced the cellular concentration of Zn and Cu. In addition, NAC inhibited the Zn-induced Nrf2 activation and limited the concomitant upregulation of cellular GSH concentrations. In contrast, mice chronically received NAC via drinking water (1 g NAC/100 mL). Cu and Zn concentrations were decreased in liver and spleen. In the duodenum, NQO1, TXNRD, and SOD activities were upregul...
Investigation of processes that contribute to the maintenance of genomic stability is one crucial... more Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage lev...
Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not a... more Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated ...
Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant e... more Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. Ho...
Plant-based diets usually contain more nutrient-dense foods such as vegetables, legumes, whole gr... more Plant-based diets usually contain more nutrient-dense foods such as vegetables, legumes, whole grains, and fruits than a standard Western diet. Yet, the amount and especially the bioavailability of several nutrients, such as trace elements, is supposed to be lower in comparison to diets with consumption of animal-derived foods. Based on this, the Nutritional Evaluation (NuEva) study (172 participants) was initiated to compare the trace element status of omnivores, flexitarians, vegetarians, and vegans. Serum selenium, zinc, and copper concentrations and biomarkers were evaluated at baseline and during a 12-month intervention with energy- and nutrient-optimized menu plans. The implementation of optimized menu plans did not substantially influence the status of trace elements. At baseline, serum selenium biomarkers were lower in vegetarians and vegans compared to omnivores and flexitarians. The zinc intake of vegetarians and vegans was significantly lower compared to omnivores, wherea...
Eine optimale Versorgung mit den essentiellen Spurenelementen Selen, Kupfer, Zink, Eisen ist wich... more Eine optimale Versorgung mit den essentiellen Spurenelementen Selen, Kupfer, Zink, Eisen ist wichtig, da sowohl eine Spurenelementdefizienz als auch eine überdosierung schwerwiegende gesundheitliche Folgen haben kann. Bereits bei der Aufnahme der Spurenelemente im Dünndarm sind gemeinsame Transportmechanismen bekannt. Weiterhin sind die vier Spurenelemente Bestandteil vieler antioxidativer Enzyme, können jedoch in hohen Konzentrationen oxidativen Stress induzieren. Alle vier Spurenelemente sind an der zellulären Redoxhomöostase beteiligt, an deren Regulation der redox-sensitive Transkriptionsfaktor Nrf2 mitwirkt. Um ein besseres Verständnis zu den Interaktionen der vier Spurenelemente untereinander und mit der Redoxhomöostase zu erlangen, wurden verschiedene Fütterungsstudien an Mäusen durchgeführt, der Einfluss eines systemischen Nrf2-KOs auf die Spurenelementhomöostase untersucht und einzelne Kombinationen der Spurenelemente in vitro analysiert. Es konnte gezeigt werden, dass alle...
Postprints der Universität Potsdam: Mathematisch-Naturwissenschaftliche Reihe, Dec 1, 2020
Investigation of processes that contribute to the maintenance of genomic stability is one crucial... more Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA da...
Selenium and iodine are among the essential trace elements. Ensuring a comprehensive, adequate su... more Selenium and iodine are among the essential trace elements. Ensuring a comprehensive, adequate supply of these elements remains a challenge across the globe to this day, despite extensive efforts (such as the iodination of table salt). Factors that play a decisive role in the supply of these nutrients include not only soil conditions and traditional foods, but also the increasing spread of dietary trends, particularly in Europe. A recently published study recorded the nutrient intakes of 32,423 study participants (EPIC-Oxford cohort) using diet questionnaires adapted to the participants’ eating habits [1]. Both, this study and similar studies conducted in Germany showed that vegetarians had a lower selenium intake than people who consume meat and fish. Vegans are particularly at risk of inadequate iodine intake (exception: those who consume seaweed) [2]. The same conclusion was drawn by studies that used biomarkers to determine the status of both of these trace elements [3, 4]. In a...
Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones bu... more Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention. Markers of the selenium status were unaffected by the iodine supply. The thyroid gland was able to maintain serum thyroxine levels even under selenium-deficient conditions, despite reduced selenoprotein expression in liver and kidney, including deiodinase type 1. Thyroid hormone target genes responded to the altered selenium and iodine supply, whereas the iron, zinc, and copper homeostasis remained unaffected. There was a notable inte...
Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping... more Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences the expression of the selenoproteome in concert with the Se supply remains obscure. THP-1 monocytes were differentiated with phorbol 12-myristate 13-acetate (PMA) into macrophages and (i) the expression of selenoproteins, (ii) differentiation markers, (iii) the activity of NF-κB and NRF2, as well as (iv) lipid mediator profiles were analyzed. Se and differentiation affected the expression of selenoproteins in a heterogeneous manner. GPX4 expression was substantially decreased during differentiation, whereas GPX1 was not affected. Moreover, Se increased the expression of selenoproteins H and F, which was further enhanced by differentiation for selenoprotein F and diminished for selenoprotein H. Notably, LPS-induced expression of NF-κB target genes was facilitated...
Purpose We aimed to examine the prospective association between manganese, iron, copper, zinc, io... more Purpose We aimed to examine the prospective association between manganese, iron, copper, zinc, iodine, selenium, selenoprotein P, free zinc, and their interplay, with incident type 2 diabetes (T2D), cardiovascular disease (CVD) and colorectal cancer (CRC). Methods Serum trace element (TE) concentrations were measured in a case-cohort study embedded within the EPIC-Potsdam cohort, consisting of a random sub-cohort (n = 2500) and incident cases of T2D (n = 705), CVD (n = 414), and CRC (n = 219). TE patterns were investigated using principal component analysis. Cox proportional hazard models were fitted to examine the association between TEs with T2D, CVD and CRC incidence. Results Higher manganese, zinc, iodine and selenium were associated with an increased risk of developing T2D (HR Q5 vs Q1: 1.56, 1.09–2.22; HR per SD, 95% CI 1.18, 1.05–1.33; 1.09, 1.01–1.17; 1.19, 1.06–1.34, respectively). Regarding CVD, manganese, copper and copper-to-zinc ratio were associated with an increased r...
N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capabili... more N-acetylcysteine (NAC) is a frequently prescribed drug and known for its metal chelating capability. However, to date it is not well characterized whether NAC intake affects the homeostasis of essential trace elements. As a precursor of glutathione (GSH), NAC also has the potential to modulate the cellular redox homeostasis. Thus, we aimed to analyze effects of acute and chronic NAC treatment on the homeostasis of copper (Cu) and zinc (Zn) and on the activity of the redox-sensitive transcription factor Nrf2. Cells were exposed to 1 mM NAC and were co-treated with 50 μM Cu or Zn. We showed that NAC treatment reduced the cellular concentration of Zn and Cu. In addition, NAC inhibited the Zn-induced Nrf2 activation and limited the concomitant upregulation of cellular GSH concentrations. In contrast, mice chronically received NAC via drinking water (1 g NAC/100 mL). Cu and Zn concentrations were decreased in liver and spleen. In the duodenum, NQO1, TXNRD, and SOD activities were upregul...
Investigation of processes that contribute to the maintenance of genomic stability is one crucial... more Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage lev...
Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not a... more Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated ...
Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant e... more Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. Ho...
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