論文 - 詳細
| RRC ID | 76010 |
|---|---|
| 著者 | Martínez-Fernández C, Bergamino M, Schiavi A, Brena D, Ventura N, Honnen S, Villanueva A, Nadal E, Cerón J. |
| タイトル | Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans. |
| ジャーナル | Dis Model Mech |
| 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 dose-dependent neurotoxicity caused by cisplatin. |
| 巻・号 | 15(3) |
| 公開日 | 2022-3-1 |
| DOI | 10.1242/dmm.049161 |
| PII | 274203 |
| PMID | 35107130 |
| PMC | PMC8995082 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans Proteins* / metabolism Cisplatin / toxicity Mitochondria / drug effects Mitochondria / metabolism Mitochondrial Diseases / chemically induced Neurotoxicity Syndromes / etiology Oxidative Stress |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 28 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm536 |