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Title: Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
Author: Martínez Fernández, Carmen
Bergamino, Milana
Schiavi, Alfonso
Brena, David
Ventura, Natascia
Honnen, Sebastian
Villanueva, Alberto
Nadal, Ernest
Cerón, Julián
Keywords: Neurotoxicologia
Issue Date: 2-Feb-2022
Publisher: Company of Biologists
Abstract: 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.
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It is part of: Disease Models & Mechanisms, 2022, vol. 15, num. 3
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ISSN: 1754-8411
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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