title: Potentiation of mutant CFTR Cl- channel currents by the naturally occurring stilbene compound resveratrol.
abstract: Previously, we found that the naturally occurring stilbene compound resveratrol (RES) could potentiate cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. Because some wild-type CFTR activators also potentiate its mutant forms, we investigated effect of RES on the two most common forms of CF-related mutation (deltaF508 and G551D-CFTR). Cell-based fluorescence studies indicated that RES dose-dependently potentiated both deltaF508 and G551D mutant CFTR Cl- channel activities. Transepithelial Cl- currents were stimulated by RES in deltaF508 and G551D mutant CFTR-expressing FRT cells. Further excised inside-out patch-clamp measurements revealed that RES significantly induced the chloride current of deltaF508 and G551D mutant CFTRs by increasing the open time of the channels. In ex vivo studies, RES stimulated fluid secretion in mouse trachea by optical measurement of single gland secretion. These data suggested that RES is a potent deltaF508 and G551D mutant CFTR potentiator, and RES may present a novel class of therapeutic lead compounds in treating cystic fibrosis.
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Yaofang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sui
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luan
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
authors.affiliation: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000235:genetics*; D007454:Iodides / Q000737:chemistry; D009154:Mutation / Q000235:genetics / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013368:Submucous Plexus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007454:Iodides; D013267:Stilbenes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000077185:Resveratrol