TY - JOUR A1 - Varão Moura, Alexandre A1 - Aparecido Rosini Silva, Alex A1 - Domingos Santo da Silva, José A1 - Aleixo Leal Pedroza, Lucas A1 - Bornhorst, Julia A1 - Stiboller, Michael A1 - Schwerdtle, Tanja A1 - Gubert, Priscila T1 - Determination of ions in Caenorhabditis elegans by ion chromatography JF - Journal of chromatography. B N2 - The Caenorhabditis elegans (C. elegans) is a model organism that has been increasingly used in health and environmental toxicity assessments. The quantification of such elements in vivo can assist in studies that seek to relate the exposure concentration to possible biological effects. Therefore, this study is the first to propose a method of quantitative analysis of 21 ions by ion chromatography (IC), which can be applied in different toxicity studies in C. elegans. The developed method was validated for 12 anionic species (fluoride, acetate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, molybdate, dichromate, phosphate, and perchlorate), and 9 cationic species (lithium, sodium, ammonium, thallium, potassium, magnesium, manganese, calcium, and barium). The method did not present the presence of interfering species, with R2 varying between 0.9991 and 0.9999, with a linear range from 1 to 100 mu g L-1. Limits of detection (LOD) and limits of quantification (LOQ) values ranged from 0.2319 mu g L-1 to 1.7160 mu g L-1 and 0.7028 mu g L-1 to 5.1999 mu g L-1, respectively. The intraday and interday precision tests showed an Relative Standard Deviation (RSD) below 10.0 % and recovery ranging from 71.0 % to 118.0 % with a maximum RSD of 5.5 %. The method was applied to real samples of C. elegans treated with 200 uM of thallium acetate solution, determining the uptake and bioaccumulated Tl+ content during acute exposure. KW - ion chromatography KW - C. elegans KW - method development KW - method validation KW - ion quantification Y1 - 2022 U6 - https://doi.org/10.1016/j.jchromb.2022.123312 SN - 1570-0232 SN - 1873-376X VL - 1204 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - GEN A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1364 KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-514995 SN - 1866-8372 IS - 8 ER - TY - JOUR A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis JF - Molecular Nutrition and Food Research N2 - Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - https://doi.org/10.1002/mnfr.202001176 SN - 1613-4133 SN - 1613-4125 VL - 65 IS - 8 SP - 1 EP - 11 PB - Wiley-VCH GmbH CY - Weinheim ER - TY - JOUR A1 - Peres, Tanara V. A1 - Horning, Kyle J. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Bowman, Aaron B. A1 - Aschner, Michael T1 - Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo JF - Biological Trace Element Research N2 - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric disturbances and may arise from an impaired or not fully developed excretion system, transporter malfunction and/or exposure to excessive levels of Mn. Therefore, deciphering processes regulating neuronal Mn homeostasis is essential to understand the mechanisms of Mn neurotoxicity. In the present study, we selected two small molecules (with opposing effects on Mn transport) from a previous high throughput screen of 40,167 to test their effects on Mn toxicity parameters in vivo using Caenorhabditis elegans. We pre-exposed worms to VU0063088 and VU0026921 for 30min followed by co-exposure for 1h with Mn and evaluated Mn accumulation, dopaminergic (DAergic) degeneration and worm survival. Control worms were exposed to vehicle (DMSO) and saline only. In pdat-1::GFP worms, with GFP labeled DAergic neurons, we observed a decrease of Mn-induced DAergic degeneration in the presence of both small molecules. This effect was also observed in an smf-2 knockout strain. SMF-2 is a regulator of Mn transport in the worms and this strain accumulates higher Mn levels. We did not observe improved survival in the presence of small molecules. Our results suggest that both VU0063088 and VU0026921 may modulate Mn levels in the worms through a mechanism that does not require SMF-2 and induce protection against Mn neurotoxicity. KW - Small molecules KW - Manganese KW - Neurotoxicity KW - C. elegans KW - Dopamine Y1 - 2018 U6 - https://doi.org/10.1007/s12011-018-1531-7 SN - 0163-4984 SN - 1559-0720 VL - 188 IS - 1 SP - 127 EP - 134 PB - Human press inc. CY - Totowa ER - TY - JOUR A1 - Ruszkiewicz, Joanna A. A1 - de Macedo, Gabriel Teixeira A1 - Miranda-Vizuete, Antonio A1 - Teixeira da Rocha, Joao B. A1 - Bowman, Aaron B. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Aschner, Michael T1 - The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner JF - Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system N2 - Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans. KW - Methylmercury KW - Age KW - Development KW - C. elegans KW - Thioredoxin KW - Thioredoxin reductase Y1 - 2018 U6 - https://doi.org/10.1016/j.neuro.2018.08.007 SN - 0161-813X SN - 1872-9711 VL - 68 SP - 189 EP - 202 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Igual Gil, Carla A1 - Jarius, Mirko A1 - von Kries, Jens P. A1 - Rohlfing, Anne-Kartin T1 - Neuronal Chemosensation and Osmotic Stress Response Converge in the Regulation of aqp-8 in C. elegans JF - Frontiers in physiology N2 - Aquaporins occupy an essential role in sustaining the salt/water balance in various cells types and tissues. Here, we present new insights into aqp-8 expression and regulation in Caenorhabditis elegans. We show, that upon exposure to osmotic stress, aqp-8 exhibits a distinct expression pattern within the excretory cell compared to other C. elegans aquaporins expressed. This expression is correlated to the osmolarity of the surrounding medium and can be activated physiologically by osmotic stress or genetically in mutants with constitutively active osmotic stress response. In addition, we found aqp-8 expression to be constitutively active in the TRPV channel mutant osm-9(ok1677). In a genome-wide RNAi screen we identified additional regulators of aqp-8. Many of these regulators are connected to chemosensation by the amphid neurons, e.g., odr-10 and gpa-6, and act as suppressors of aqp-8 expression. We postulate from our results, that aqp-8 plays an important role in sustaining the salt/water balance during a secondary response to hyper-osmotic stress. Upon its activation aqp-8 promotes vesicle docking to the lumen of the excretory cell and thereby enhances the ability to secrete water and transport osmotic active substances or waste products caused by protein damage. In summary, aqp-8 expression and function is tightly regulated by a network consisting of the osmotic stress response, neuronal chemosensation as well as the response to protein damage. These new insights in maintaining the salt/water balance in C. elegans will help to reveal the complex homeostasis network preserved throughout species. KW - aquaporin KW - osmoregulation KW - osmotic stress KW - chemosensation KW - C. elegans Y1 - 2017 U6 - https://doi.org/10.3389/fphys.2017.00380 SN - 1664-042X VL - 8 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Jedrusik-Bode, Monika A1 - Studencka, Maja A1 - Smolka, Christian A1 - Baumann, Tobias A1 - Schmidt, Henning A1 - Kampf, Jan A1 - Paap, Franziska A1 - Martin, Sophie A1 - Tazi, Jamal A1 - Müller, Kristian M. A1 - Krüger, Marcus A1 - Braun, Thomas A1 - Bober, Eva T1 - The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals JF - Journal of cell science N2 - SIRT6 is a NAD(+)-dependent deacetylase that modulates chromatin structure and safeguards genomic stability. Until now, SIRT6 has been assigned to the nucleus and only nuclear targets of SIRT6 are known. Here, we demonstrate that in response to stress, C. elegans SIR-2.4 and its mammalian orthologue SIRT6 localize to cytoplasmic stress granules, interact with various stress granule components and induce their assembly. Loss of SIRT6 or inhibition of its catalytic activity in mouse embryonic fibroblasts impairs stress granule formation and delays disassembly during recovery, whereas deficiency of SIR-2.4 diminishes maintenance of P granules and decreases survival of C. elegans under stress conditions. Our findings uncover a novel, evolutionary conserved function of SIRT6 in the maintenance of stress granules in response to stress. KW - C. elegans KW - G3BP KW - SIRT6 KW - Sirtuins KW - Stress KW - Stress granules Y1 - 2013 U6 - https://doi.org/10.1242/jcs.130708 SN - 0021-9533 SN - 1477-9137 VL - 126 IS - 22 SP - 5166 EP - + PB - Company of Biologists Limited CY - Cambridge ER -