Journal of Bioenergetics and Biomembranes

, Volume 50, Issue 2, pp 117–129 | Cite as

Aberrant GSH reductase and NOX activities concur with defective CFTR to pro-oxidative imbalance in cystic fibrosis airways

  • L. de Bari
  • M. Favia
  • A. Bobba
  • R. Lassandro
  • L. Guerra
  • A. Atlante


Cystic fibrosis (CF) is associated to impaired Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel also causing decreased glutathione (GSH) secretion, defective airway bacterial clearance and inflammation. Here we checked the main ROS-producing and ROS-scavenging enzymes as potential additional factors involved in CF pathogenesis. We found that CFBE41o-cells, expressing F508del CFTR, have increased NADPH oxidase (NOX) activity and expression level, mainly responsible of the increased ROS production, and decreased glutathione reductase (GR) activity, not dependent on GR protein level decrease. Furthermore, defective CFTR proved to cause both extracellular and intracellular GSH level decrease, probably by reducing the amount of extracellular GSH-derived cysteine required for cytosolic GSH synthesis. Importantly, we provide evidence that defective CFTR and NOX/GR activity imbalance both contribute to NADPH and GSH level decrease and ROS overproduction in CF cells.


Cystic fibrosis Mitochondria NADPH oxidase Glutathione reductase Cysteine 





Alcohol dehydrogenase




Antioxidant system


Airway surface liquid


Cystic Fibrosis


CFBE41o-cells expressing F508del CFTR


Cystic Fibrosis Transmembrane Conductance Regulator


Mitochondrial Complex IV






Cytochrome P450


Dimethyl sulfoxide




5,5′-dithio-bis(2-nitrobenzoic acid)


Dual oxidase 1


Dual oxidase 2


Extracellular GSH


Glutathione peroxidase


Glutathione reductase


Reduced glutathione


Glutathione disulfide




Hydrogen peroxide


Intracellular GSH


N(ω)-nitro-L-arginine methyl ester


mitochondrial Complex I




3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide




NAD(P)H oxidases


Superoxide anion radical


Phosphate-buffered saline


Phenazine ethosulfate


Reactive oxygen species




Standard deviation


5′-thio-2-nitrobenzoic acid


CFBE41o-cells stably expressing wildtype CFTR


Xanthine oxidase



This research was supported by Italian Cystic Fibrosis Research Foundation with the contribution of “Infront e Play for Change” and “Gare di golf” (FFC#1/2015 Project: “Relationship between mitochondria and F508del-CFTR in Cystic Fibrosis”) to A.A.

M.F. has been PostDoc fellow of the Italian Cystic Fibrosis Research Foundation.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari (IBIOM) – CNRBariItaly
  2. 2.Dipartimento di BioscienzeBiotecnologie e Biofarmaceutica - Università di BariBariItaly
  3. 3.Istituto di Cristallografia (IC) – CNRBariItaly

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