Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C elegans to explore cisplatin effects...

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Autores: Martínez Fernández, Carmen, Bergamino Sirvén, Milana, Schiavi, Alfonso, Brena, David, Ventura, Natascia, Honnen, Sebastian, Villanueva, Alberto, Nadal, Ernest, Cerón Madrigal, Julián
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/185292
Acesso em linha:https://hdl.handle.net/2445/185292
Access Level:acceso abierto
Palavra-chave:Neurotoxicologia
Mitocondris
Neurotoxicology
Mitochondria
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spelling Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegansMartínez Fernández, CarmenBergamino Sirvén, MilanaSchiavi, AlfonsoBrena, DavidVentura, NatasciaHonnen, SebastianVillanueva, AlbertoNadal, ErnestCerón Madrigal, JuliánNeurotoxicologiaMitocondrisNeurotoxicologyMitochondriaCisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. First, we report that a high-glucose diet sensitizes C elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse XFe96 Analyzer, we observed a detrimental effect of cisplatin and glucose on mitochondrial respiration. Second, because catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. Using a Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects against the doseoependent neurotoxicity caused by cisplatin.Company of Biologists2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/185292Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1242/dmm.049161Disease Models & Mechanisms, 2022, vol. 15, num. 3https://doi.org/10.1242/dmm.049161cc by (c) Martínez Fernández, Carmen et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1852922026-05-27T06:46:51Z
dc.title.none.fl_str_mv Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
title Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
spellingShingle Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
Martínez Fernández, Carmen
Neurotoxicologia
Mitocondris
Neurotoxicology
Mitochondria
title_short Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
title_full Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
title_fullStr Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
title_full_unstemmed Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
title_sort Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
dc.creator.none.fl_str_mv Martínez Fernández, Carmen
Bergamino Sirvén, Milana
Schiavi, Alfonso
Brena, David
Ventura, Natascia
Honnen, Sebastian
Villanueva, Alberto
Nadal, Ernest
Cerón Madrigal, Julián
author Martínez Fernández, Carmen
author_facet Martínez Fernández, Carmen
Bergamino Sirvén, Milana
Schiavi, Alfonso
Brena, David
Ventura, Natascia
Honnen, Sebastian
Villanueva, Alberto
Nadal, Ernest
Cerón Madrigal, Julián
author_role author
author2 Bergamino Sirvén, Milana
Schiavi, Alfonso
Brena, David
Ventura, Natascia
Honnen, Sebastian
Villanueva, Alberto
Nadal, Ernest
Cerón Madrigal, Julián
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurotoxicologia
Mitocondris
Neurotoxicology
Mitochondria
topic Neurotoxicologia
Mitocondris
Neurotoxicology
Mitochondria
description Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. First, we report that a high-glucose diet sensitizes C elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse XFe96 Analyzer, we observed a detrimental effect of cisplatin and glucose on mitochondrial respiration. Second, because catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. Using a Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects against the doseoependent neurotoxicity caused by cisplatin.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/185292
url https://hdl.handle.net/2445/185292
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1242/dmm.049161
Disease Models & Mechanisms, 2022, vol. 15, num. 3
https://doi.org/10.1242/dmm.049161
dc.rights.none.fl_str_mv cc by (c) Martínez Fernández, Carmen et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Martínez Fernández, Carmen et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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