CFTR Is Involved in the Fine Tuning of Intracellular Redox Status
| العنوان: | CFTR Is Involved in the Fine Tuning of Intracellular Redox Status |
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| المؤلفون: | Marc Cougnon, Nicolas Melis, Christophe Duranton, Baharia Mograbi, Isabelle Rubera, Abderrahman Chargui, Michel Tauc |
| المساهمون: | Transport Ionique Aspects Normaux et Pathologiques (TIANP), CNRS, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Physiologie cellulaire et moléculaire des systèmes intégrés (PCMSI), 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| المصدر: | American Journal of Pathology American Journal of Pathology, American Society for Investigative Pathology, 2012, 181 (4), pp.1367-1377. ⟨10.1016/j.ajpath.2012.06.017⟩ |
| بيانات النشر: | HAL CCSD, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | MESH: Oxidation-Reduction, [SDV]Life Sciences [q-bio], Cell, MESH: Cell Hypoxia, Regulator, Cystic fibrosis, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Osmolar Concentration, MESH: Animals, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, MESH: Glutathione, 0303 health sciences, Kidney, MESH: Reactive Oxygen Species, 3. Good health, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Intracellular Space, medicine.symptom, Intracellular, medicine.medical_specialty, MESH: Mutation, MESH: Carbonic Anhydrases, MESH: Cystic Fibrosis, Biology, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, Pathology and Forensic Medicine, 03 medical and health sciences, MESH: Acetylcysteine, MESH: Green Fluorescent Proteins, MESH: Kidney Tubules, Proximal, MESH: Mice, Inbred C57BL, Internal medicine, MESH: Protein Stability, medicine, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Chloride Channels, MESH: Models, Biological, Glutathione, Hypoxia (medical), medicine.disease, MESH: Male, MESH: Cell Line, Endocrinology, chemistry, Cell culture, MESH: Disease Models, Animal |
| الوصف: | International audience; Adaptation to hypoxia is an essential physiological response to decrease in tissue oxygenation. This process is primarily under the control of transcriptional activator hypoxia-inducible factor (HIF1). A better understanding of the intracellular HIF1 stabilization pathway would help in management of various diseases characterized by anemia. Among human pathologies, cystic fibrosis disease is characterized by a chronic anemia that is inadequately compensated by the classical erythroid response mediated by the HIF pathway. Because the kidney expresses CFTR and is a master organ involved in the adaptation to hypoxia, we used renal cells to explore the relationship between CFTR and the HIF1-mediated pathway. To monitor the adaptive response to hypoxia, we engineered a hypoxia-induced fluorescent reporter system to determine whether CFTR modulates hypoxia-induced HIF1 stabilization. We show that CFTR is a regulator of HIF stabilization by controlling the intracellular reactive oxygen species (ROS) level through its ability to transport glutathione (a ROS scavenger) out of the cell. Moreover, we demonstrated in a mouse model that both the pharmacological inhibition and the ΔF508 mutation of CFTR lead to an impairment of the adaptive erythroid response to oxygen deprivation. We conclude that CFTR controls HIF stabilization through control of the level of intracellular ROS that act as signaling agents in the HIF-1 pathway. |
| اللغة: | English |
| تدمد: | 0002-9440 1525-2191 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d08af3c77280c5f2d0cd3caa3fc7ae66Test https://hal.archives-ouvertes.fr/hal-02466034Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d08af3c77280c5f2d0cd3caa3fc7ae66 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029440 15252191 |
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