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 - JOUR A1 - Chen, Pan A1 - Bornhorst, Julia A1 - Aschner, Michael T1 - Manganese metabolism in humans JF - Frontiers in Bioscience-Landmark N2 - Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism. KW - Manganese KW - Metal Metabolism KW - Homeostasis KW - Blood-Brain Barrier KW - Neurotoxicity KW - Transporters KW - Review Y1 - 2018 U6 - https://doi.org/10.2741/4665 SN - 1093-9946 SN - 1093-4715 VL - 23 IS - 9 SP - 1655 EP - 1679 PB - Frontiers in Bioscience INC CY - Irvine ER - TY - GEN A1 - Chen, Pan A1 - Bornhorst, Julia A1 - Aschner, Michael A. T1 - Manganese metabolism in humans T2 - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe N2 - Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 711 KW - Manganese KW - Metal Metabolism KW - Homeostasis KW - Blood-Brain Barrier KW - Neurotoxicity KW - Transporters KW - Review Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427432 SN - 1866-8372 IS - 711 ER - TY - JOUR A1 - Gubert, Priscila A1 - Puntel, Bruna A1 - Lehmen, Tassia A1 - Fessel, Joshua P. A1 - Cheng, Pan A1 - Bornhorst, Julia A1 - Trindade, Lucas Siqueira A1 - Avila, Daiana S. A1 - Aschner, Michael A1 - Soares, Felix A. A. T1 - Metabolic effects of manganese in the nematode Caenorhabditis elegans through DAergic pathway and transcription factors activation JF - Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system N2 - Manganese (Mn) is an essential trace element for physiological functions since it acts as an enzymatic co-factor. Nevertheless, overexposure to Mn has been associated with a pathologic condition called manganism. Furthermore, Mn has been reported to affect lipid metabolism by mechanisms which have yet to be established. Herein, we used the nematode Caenorhabditis elegans to examine Mn’s effects on the dopaminergic (DAergic) system and determine which transcription factors that regulate with lipid metabolism are affected by it. Worms were exposed to Mn for four hours in the presence of bacteria and in a liquid medium (85 mM NaCl). Mn increased fat storage as evidenced both by Oil Red O accumulation and triglyceride levels. In addition, metabolic activity was reduced as a reflection of decreased oxygen consumption caused by Mn. Mn also affected feeding behavior as evidenced by decreased pharyngeal pumping rate. DAergic neurons viability were not altered by Mn, however the dopamine levels were significantly reduced following Mn exposure. Furthermore, the expression of sbp-1 transcription factor and let-363 protein kinase responsible for lipid accumulation control was increased and decreased, respectively, by Mn. Altogether, our data suggest that Mn increases the fat storage in C. elegans, secondary to DAergic system alterations, under the control of SBP-1 and LET-363 proteins. KW - Manganese KW - Caenorhabditis elegans KW - Lipid metabolism KW - Dopaminergic system KW - Manganism Y1 - 2018 U6 - https://doi.org/10.1016/j.neuro.2018.04.008 SN - 0161-813X SN - 1872-9711 VL - 67 SP - 65 EP - 72 PB - Elsevier CY - Amsterdam ER -