title: Resveratrol rescues cAMP-dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These results show that resveratrol modulated CFTR expression and localization and could rescue cAMP-dependent chloride transport in delF508CFTR cells.
authors.affiliation: Inserm U, Paris, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Hamdaoui
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Baudoin-Legros
authors.forename: Mairead
authors.initials: M
authors.lastname: Kelly
authors.forename: Abdel
authors.initials: A
authors.lastname: Aissat
authors.forename: Sandra
authors.initials: S
authors.lastname: Moriceau
authors.forename: Diane-Lore
authors.initials: DL
authors.lastname: Vieu
authors.forename: Julien
authors.initials: J
authors.lastname: Colas
authors.forename: Janine
authors.initials: J
authors.lastname: Fritsch
authors.forename: Aleksander
authors.initials: A
authors.lastname: Edelman
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Planelles
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D027321:Anion Transport Proteins; D018118:Chloride Channels; D016209:Interleukin-8; D013267:Stilbenes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D000077185:Resveratrol