Thallium Toxicity inCaenorhabditis elegans: Involvement of the SKN-1 Pathway and Protection byS-Allylcysteine
| Autor: | Rubén Estrada-Valencia, Isaac Túnez, Çimen Karasu, María Ester Hurtado-Díaz, Alinne Colonnello, Marisol Maya-López, Abel Santamaría, Sandra V. Verstraeten, Michael Aschner, Edgar Rangel-López, Sonia Galván-Arzate |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antioxidant medicine.medical_treatment Mutant Longevity Toxicology Antioxidants Animals Genetically Modified 03 medical and health sciences chemistry.chemical_compound Gene Knockout Techniques 0302 clinical medicine In vivo medicine Organometallic Compounds Animals Body Size Cysteine Caenorhabditis elegans Caenorhabditis elegans Proteins Glutathione Transferase biology Chemistry General Neuroscience Glutathione biology.organism_classification Cell biology DNA-Binding Proteins 030104 developmental biology Nematode Toxicity Signal transduction 030217 neurology & neurosurgery Transcription Factors |
| Popis: | Monovalent thallium (Tl+) is a cation that can exert complex neurotoxic patterns in the brain by mechanisms that have yet to be completely characterized. To learn more about Tl+ toxicity, it is necessary to investigate its major effects in vivo and its ability to trigger specific signaling pathways (such as the antioxidant SKN-1 pathway) in different biological models. Caenorhabditis elegans (C. elegans) is a nematode constituting a simple in vivo biological model with a well-characterized nervous system, and high genetic homology to mammalian systems. In this study, both wild-type (N2) and skn-1 knockout (KO) mutant C. elegans strains subjected to acute and chronic exposures to Tl+ [2.5–35 μM] were evaluated for physiological stress (survival, longevity, and worm size), motor alterations (body bends), and biochemical changes (glutathione S-transferase regulation in a gst-4 fluorescence strain). While survival was affected by Tl+ in N2 and skn-1 KO (worms lacking the orthologue of mammalian Nrf2) strains in a similar manner, the longevity was more prominently decreased in the skn-1 KO strain compared with the wild-type strain. Moreover, chronic exposure led to a greater compromise in the longevity in both strains compared with acute exposure. Tl+ also induced motor alterations in both skn-1 KO and wild-type strains, as well as changes in worm size in wild-type worms. In addition, preconditioning nematodes with the well-known antioxidant S-allylcysteine (SAC) reversed the Tl+-induced decrease in survival in the N2 strain. GST fluorescent expression was also decreased by the metal in the nematode, and recovered by SAC. Our results describe and validate, for the first time, features of the toxic pattern induced by Tl+ in an in vivo biological model established with C. elegans, supporting an altered redox component in Tl+ toxicity, as previously described in mammal models. We demonstrate that the presence of the orthologous SKN-1 pathway is required for worms in evoking an efficient antioxidant defense. Therefore, the nematode represents an optimal model to reproduce mammalian Tl+ toxicity, where toxic mechanisms and novel therapeutic approaches of clinical value may be successfully pursued. |
| Databáze: | OpenAIRE |
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