Role of CFTR in oxidative stress and suicidal death of renal cells during cisplatin-induced nephrotoxicity
| Autor: | Marc Cougnon, Isabelle Rubera, Baharia Mograbi, Nicolas Melis, Christophe Duranton, Michel Tauc |
|---|---|
| Přispěvatelé: | Physiologie cellulaire et moléculaire des systèmes intégrés (PCMSI), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
MESH: Cell Death
Cancer Research [SDV]Life Sciences [q-bio] Intracellular Space Cystic Fibrosis Transmembrane Conductance Regulator Pharmacology Kidney medicine.disease_cause Benzoates Kidney Tubules Proximal DNA Adducts Mice 0302 clinical medicine MESH: Caspase 3 MESH: Animals NGAL chemistry.chemical_classification MESH: Glutathione MESH: Cystic Fibrosis Transmembrane Conductance Regulator 0303 health sciences MESH: Oxidative Stress Cell Death biology Caspase 3 apoptosis MESH: Reactive Oxygen Species respiratory system Glutathione Cystic fibrosis transmembrane conductance regulator 3. Good health medicine.anatomical_structure Biochemistry MESH: Cell Survival 030220 oncology & carcinogenesis kidney injury Thiazolidines MESH: Intracellular Space Original Article Female Kidney Diseases MESH: Thiazolidines Intracellular MESH: DNA Adducts medicine.drug MESH: Enzyme Activation MESH: Cell Line Tumor MESH: Rats Cell Survival Immunology Nephrotoxicity 03 medical and health sciences Cellular and Molecular Neuroscience CFTRinh-172 MESH: Kidney Tubules Proximal Cell Line Tumor GSH medicine cancer Animals Humans Rats Wistar MESH: Mice Platinum 030304 developmental biology Cisplatin Reactive oxygen species MESH: Kidney Diseases MESH: Humans Body Weight MESH: Platinum Cell Biology MESH: Kidney MESH: Rats Wistar MESH: Benzoates Rats respiratory tract diseases MESH: Body Weight Enzyme Activation Oxidative Stress chemistry MESH: Cisplatin Apoptosis biology.protein MESH: Biomarkers Reactive Oxygen Species MESH: Female Biomarkers Oxidative stress |
| Zdroj: | Cell Death and Disease Cell Death and Disease, Nature Publishing Group, 2013, 4 (10), pp.e817-e817. ⟨10.1038/cddis.2013.355⟩ Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2013.355⟩ |
| Popis: | International audience; The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic fibrosis transmembrane conductance regulator protein (CFTR), a Cl(-) channel not only involved in chloride secretion but as well in glutathione (GSH) transport. Thus, we tested whether the inhibition of CFTR could protect against cisplatin-induced nephrotoxicity. Using a renal proximal cell line, we show that the specific inhibitor of CFTR, CFTR(inh)-172, prevents cisplatin-induced cell death and apoptosis by modulating the intracellular reactive oxygen species balance and the intracellular GSH concentration. This CFTR(inh)-172-mediated protective effect occurs without affecting cellular cisplatin uptake or the formation of platinum-DNA adducts. The protective effect of CFTR(inh)-172 in cisplatin-induced nephrotoxicity was also investigated in a rat model. Five days after receiving a single cisplatin injection (5 mg/kg), rats exhibited renal failure, as evidenced by the alteration of biochemical and functional parameters. Pretreatment of rats with CFTR(inh)-172 (1 mg/kg) prior to cisplatin injection significantly prevented these deleterious cisplatin-induced nephrotoxic effects. Finally, we demonstrate that CFTR(inh)-172 does not impair cisplatin-induced cell death in the cisplatin-sensitive A549 cancer cell line. In conclusion, the use of a specific inhibitor of CFTR may represent a novel therapeutic approach in the prevention of nephrotoxic side effects during cisplatin treatment without affecting its antitumor efficacy. |
| Databáze: | OpenAIRE |
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