TY - JOUR A1 - Wandt, Viktoria Klara Veronika A1 - Winkelbeiner, Nicola Lisa A1 - Bornhorst, Julia A1 - Witt, Barbara A1 - Raschke, Stefanie A1 - Simon, Luise A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A matter of concern BT - trace element dyshomeostasis and genomic stability in neurons JF - Redox Biology N2 - Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability Y1 - 2021 U6 - https://doi.org/10.1016/j.redox.2021.101877 VL - 41 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Witt, B. A1 - Bornhorst, Julia A1 - Mitze, H. A1 - Ebert, Franziska A1 - Meyer, S. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as compared to the respective monocultures JF - Metallomics : integrated biometal science N2 - Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons. Notably the AsHCs did not show any substantial toxic effects in the co-culture, while arsenite did. The arsenic accessibility studies indicated that in the co-culture astrocytes protect neurons against cellular arsenic accumulation especially after incubation with arsenolipids. In summary, these data underline the importance of the glial-neuron interaction when assessing the in vitro neurotoxicity of new unclassified metal species. Y1 - 2017 U6 - https://doi.org/10.1039/c7mt00036g SN - 1756-5901 SN - 1756-591X VL - 9 SP - 442 EP - 446 PB - Royal Society of Chemistry CY - Cambridge 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 - JOUR A1 - Jacques, Mauricio Tavares A1 - Bornhorst, Julia A1 - Soares, Marcell Valandro A1 - Schwerdtle, Tanja A1 - Garcia, Solange A1 - Avila, Daiana Silva T1 - Reprotoxicity of glyphosate-based formulation in Caenorhabditis elegans is not due to the active ingredient only JF - Environmental pollution N2 - Pesticides guarantee us high productivity in agriculture, but the long-term costs have proved too high. Acute and chronic intoxication of humans and animals, contamination of soil, water and food are the consequences of the current demand and sales of these products. In addition, pesticides such as glyphosate are sold in commercial formulations which have inert ingredients, substances with unknown composition and proportion. Facing this scenario, toxicological studies that investigate the interaction between the active principle and the inert ingredients are necessary. The following work proposed comparative toxicology studies between glyphosate and its commercial formulation using the alternative model Caenorhabditis elegans. Worms were exposed to different concentrations of the active ingredient (glyphosate in monoisopropylamine salt) and its commercial formulation. Reproductive capacity was evaluated through brood size, morphological analysis of oocytes and through the MD701 strain (bcIs39), which allows the visualization of germ cells in apoptosis. In addition, the metal composition in the commercial formulation was analyzed by ICP-MS. Only the commercial formulation of glyphosate showed significant negative effects on brood size, body length, oocyte size, and the number of apoptotic cells. Metal analysis showed the presence of Hg, Fe, Mn, Cu, Zn, As, Cd and Pb in the commercial formulation, which did not cause reprotoxicity at the concentrations found. However, metals can bio-accumulate in soil and water and cause environmental impacts. Finally, we demonstrated that the addition of inert ingredients increased the toxic profile of the active ingredient glyphosate in C. elegans, which reinforces the need of components description in the product labels. (C) 2019 Elsevier Ltd. All rights reserved. KW - Glyphosate KW - Inert ingredients KW - Reproduction KW - Oocytes KW - Development KW - Metals Y1 - 2019 U6 - https://doi.org/10.1016/j.envpol.2019.06.099 SN - 0269-7491 SN - 1873-6424 VL - 252 SP - 1854 EP - 1862 PB - Elsevier CY - Oxford ER -