CFTR mediates cadmium-induced apoptosis through modulation of ROS level in mouse proximal tubule cells

Autor: Abderrahmen Chargui, Philippe Poujeol, Chantal Poujeol, Isabelle Rubera, Michel Tauc, Radia Belfodil, Sebastien L'hoste, Christophe Duranton, Baharia Mograbi
Přispěvatelé: Transduction du signal et oncogénèse, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire de PhysioMédecine Moléculaire (LP2M), 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)-Université Côte d'Azur (UCA), 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), Laboratoire CNRS 3093, Université de Nice-Sophia Antipolis, Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
congenital
hereditary
and neonatal diseases and abnormalities
Patch-Clamp Techniques
Necrosis
Cystic Fibrosis
[SDV]Life Sciences [q-bio]
Cell Culture Techniques
Cystic Fibrosis Transmembrane Conductance Regulator
Apoptosis
Benzoates
Biochemistry
Membrane Potentials
Kidney Tubules
Proximal
Mice
03 medical and health sciences
chemistry.chemical_compound
Potassium Channels
Tandem Pore Domain
0302 clinical medicine
Physiology (medical)
medicine
Animals
Mice
Inbred CFTR
Patch clamp
Extracellular Signal-Regulated MAP Kinases
ComputingMilieux_MISCELLANEOUS
Cell Line
Transformed
Cell Size
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Reactive oxygen species
Caspase 3
Glutathione
respiratory system
Molecular biology
digestive system diseases
Potassium channel
respiratory tract diseases
chemistry
Cell culture
030220 oncology & carcinogenesis
Thiazolidines
medicine.symptom
Reactive Oxygen Species
Intracellular
Cadmium
Signal Transduction
Zdroj: Free Radical Biology and Medicine
Free Radical Biology and Medicine, Elsevier, 2009, 46 (8), pp.1017-1031. ⟨10.1016/j.freeradbiomed.2008.12.009⟩
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2008.12.009⟩
Popis: The aim of this study was to characterize the role of CFTR during Cd(2+)-induced apoptosis. For this purpose primary cultures and cell lines originated from proximal tubules (PCT) of wild-type cftr(+/+) and cftr(-/-) mice were used. In cftr(+/+) cells, the application of Cd(2+) (5 microM) stimulated within 8 min an ERK1/2-activated CFTR-like Cl(-) conductance sensitive to CFTR(inh)-172. Thereafter Cd(2+) induced an apoptotic volume decrease (AVD) within 6 h followed by caspase-3 activation and apoptosis. The early increase in CFTR conductance was followed by the activation of volume-sensitive outwardly rectifying (VSOR) Cl(-) and TASK2 K(+) conductances. By contrast, cftr(-/-) cells exposed to Cd(2+) were unable to develop VSOR currents, caspase-3 activity, and AVD process and underwent necrosis. Moreover in cftr(+/+) cells, Cd(2+) enhanced reactive oxygen species (ROS) production and induced a 50% decrease in total glutathione content (major ROS scavenger in PCT). ROS generation and glutathione decrease depended on the presence of CFTR, since they did not occur in the presence of CFTR(inh)-172 or in cftr(-/-) cells. Additionally, Cd(2+) exposure accelerates effluxes of fluorescent glutathione S-conjugate in cftr(+/+) cells. Our data suggest that CFTR could modulate ROS levels to ensure apoptosis during Cd(2+) exposure by modulating the intracellular content of glutathione.
Databáze: OpenAIRE
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