Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i>
Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/20/10905 |
| _version_ | 1797514404634296320 |
|---|---|
| author | Merle M. Nicolai Ann-Kathrin Weishaupt Jessica Baesler Vanessa Brinkmann Anna Wellenberg Nicola Winkelbeiner Anna Gremme Michael Aschner Gerhard Fritz Tanja Schwerdtle Julia Bornhorst |
| author_facet | Merle M. Nicolai Ann-Kathrin Weishaupt Jessica Baesler Vanessa Brinkmann Anna Wellenberg Nicola Winkelbeiner Anna Gremme Michael Aschner Gerhard Fritz Tanja Schwerdtle Julia Bornhorst |
| author_sort | Merle M. Nicolai |
| collection | DOAJ |
| description | Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism <i>Caenorhabditis elegans</i> to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) <i>parg-1</i> or <i>parg-2</i> (two orthologue of PARG), indicates that <i>parg-1</i> accounts for most of the glycohydrolase activity in worms. |
| first_indexed | 2024-03-10T06:31:09Z |
| format | Article |
| id | doaj.art-d3307c0e15894106b547e00213dc8b52 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:31:09Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d3307c0e15894106b547e00213dc8b522023-11-22T18:30:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201090510.3390/ijms222010905Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i>Merle M. Nicolai0Ann-Kathrin Weishaupt1Jessica Baesler2Vanessa Brinkmann3Anna Wellenberg4Nicola Winkelbeiner5Anna Gremme6Michael Aschner7Gerhard Fritz8Tanja Schwerdtle9Julia Bornhorst10Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, GermanyFood Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal, 14558 Nuthetal, GermanyInstitute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstr.5, 40225 Düsseldorf, GermanyInstitute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstr.5, 40225 Düsseldorf, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal, 14558 Nuthetal, GermanyFood Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, GermanyAlbert Einstein College of Medicine, Department of Molecular Pharmacology, Neuroscience and Pediatrics, Bronx, NY 10032, USAInstitute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstr.5, 40225 Düsseldorf, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal, 14558 Nuthetal, GermanyFood Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, GermanyAlthough manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism <i>Caenorhabditis elegans</i> to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) <i>parg-1</i> or <i>parg-2</i> (two orthologue of PARG), indicates that <i>parg-1</i> accounts for most of the glycohydrolase activity in worms.https://www.mdpi.com/1422-0067/22/20/10905manganeseoxidative stressDNA repairDNA damage response<i>Caenorhabditis elegans</i> |
| spellingShingle | Merle M. Nicolai Ann-Kathrin Weishaupt Jessica Baesler Vanessa Brinkmann Anna Wellenberg Nicola Winkelbeiner Anna Gremme Michael Aschner Gerhard Fritz Tanja Schwerdtle Julia Bornhorst Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> International Journal of Molecular Sciences manganese oxidative stress DNA repair DNA damage response <i>Caenorhabditis elegans</i> |
| title | Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> |
| title_full | Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> |
| title_fullStr | Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> |
| title_full_unstemmed | Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> |
| title_short | Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i> |
| title_sort | effects of manganese on genomic integrity in the multicellular model organism i caenorhabditis elegans i |
| topic | manganese oxidative stress DNA repair DNA damage response <i>Caenorhabditis elegans</i> |
| url | https://www.mdpi.com/1422-0067/22/20/10905 |
| work_keys_str_mv | AT merlemnicolai effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT annkathrinweishaupt effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT jessicabaesler effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT vanessabrinkmann effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT annawellenberg effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT nicolawinkelbeiner effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT annagremme effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT michaelaschner effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT gerhardfritz effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT tanjaschwerdtle effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi AT juliabornhorst effectsofmanganeseongenomicintegrityinthemulticellularmodelorganismicaenorhabditiselegansi |