Ouabain Mimics Low Temperature Rescue of F508del-CFTR in Cystic Fibrosis Epithelial Cells

• Published in: Frontiers in pharmacology 2012-01, Vol.3, p.176-176
• Main Authors: Zhang, Donglei, Ciciriello, Fabiana, Anjos, Suzana M, Carissimo, Annamaria, Liao, Jie, Carlile, Graeme W, Balghi, Haouaria, Robert, Renaud, Luini, Alberto, Hanrahan, John W, Thomas, David Y
• Format: Article
• Language: English
• Subjects: CFTR; Cystic Fibrosis; hierarchical clustering; Microarray; Ouabain; Pharmacology; trafficking
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2012.00176

Most cases of cystic fibrosis (CF) are caused by the deletion of a single phenylalanine residue at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutant F508del-CFTR is retained in the endoplasmic reticulum and degraded, but can be induced by low temperature incubation (29°C) to traffic to the plasma membrane where it functions as a chloride channel. Here we show that, cardiac glycosides, at nanomolar concentrations, can partially correct the trafficking of F508del-CFTR in human CF bronchial epithelial cells (CFBE41o-) and in an F508del-CFTR mouse model. Comparison of the transcriptional profiles obtained with polarized CFBE41o-cells after treatment with ouabain and by low temperature has revealed a striking similarity between the two corrector treatments that is not shared with other correctors. In summary, our study shows a novel function of ouabain and its analogs in the regulation of F508del-CFTR trafficking and suggests that compounds that mimic this low temperature correction of trafficking will provide new avenues for the development of therapeutics for CF.