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Resveratrol rescues cAMP‐dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1
Author(s) -
Hamdaoui Nabila,
BaudoinLegros Maryvonne,
Kelly Mairead,
Aissat Abdel,
Moriceau Sandra,
Vieu DianeLore,
Colas Julien,
Fritsch Janine,
Edelman Aleksander,
Planelles Gabrielle
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01289.x
Subject(s) - cystic fibrosis transmembrane conductance regulator , chloride channel , resveratrol , cystic fibrosis , microbiology and biotechnology , chemistry , western blot , cell culture , immunocytochemistry , biology , biochemistry , endocrinology , gene , genetics
BACKGROUND AND PURPOSE The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP‐dependent chloride channel in the plasma membrane of epithelia whose mutation is the cause of the genetic disease cystic fibrosis (CF). The most frequent CFTR mutation is deletion of Phe 508 and this mutant protein (delF508CFTR) does not readily translocate to the plasma membrane and is rapidly degraded within the cell. We hypothesized that treating epithelial cells with resveratrol, a natural polyphenolic, phyto‐ooestrogenic compound from grapes, could modulate both the expression and localization of CFTR. EXPERIMENTAL APPROACH Cells endogenously expressing CFTR (MDCK1 and CAPAN1 cells) or delF508CFTR (CFPAC1 and airway epithelial cells, deriving from human bronchial biopsies) were treated with resveratrol for 2 or 18 h. The effect of this treatment on CFTR and delF508CFTR expression and localization was evaluated using RT‐PCR, Western blot and immunocytochemistry. Halide efflux was measured with a fluorescent dye and with halide‐sensitive electrodes. Production of interleukin‐8 by these cells was assayed by ELISA. KEY RESULTS Resveratrol treatment increased CFTR expression or maturation in immunoblotting experiments in MDCK1 cells or in CFPAC1 cells. Indirect immunofluorescence experiments showed a shift of delF508CFTR localization towards the (peri)‐membrane area in CFPAC1 cells and in human airway epithelial cells. A cAMP‐dependent increase in membrane permeability to halide was detected in resveratrol‐treated CFPAC1 cells, and was inhibited by a selective inhibitor of CFTR. CONCLUSION AND IMPLICATIONS These results show that resveratrol modulated CFTR expression and localization and could rescue cAMP‐dependent chloride transport in delF508CFTR cells.