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Author Wang, Xue ♦ Zhang, Yao-Fang ♦ Yu, Bo ♦ Yang, Shuang ♦ Luan, Jian ♦ Liu, Xin ♦ Yang, Hong
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Taylor & Francis
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Natural sciences & mathematics ♦ Chemistry & allied sciences ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Genetics and evolution ♦ Natural history of organisms ♦ Technology ♦ Medicine & health ♦ Human physiology ♦ Pharmacology and therapeutics
Subject Domain (in MeSH) Eukaryota ♦ Organisms ♦ Organic Chemicals ♦ Amino Acids, Peptides, and Proteins ♦ Chemicals and Drugs ♦ Genetic Phenomena ♦ Biological Sciences
Subject Keyword Discipline Chemistry ♦ Discipline Pharmacology ♦ Cystic Fibrosis Transmembrane Conductance Regulator ♦ Metabolism ♦ Lactones ♦ Pharmacology ♦ Sesquiterpenes ♦ Animals ♦ Colforsin ♦ Drug Effects ♦ Genetics ♦ Mice ♦ Mutation ♦ Rats ♦ Journal Article ♦ Research Support, Non-u.s. Gov't
Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) represents the main cAMP-activated Clâ » channel expressed in the apical membrane of serous epithelial cells. Both deficiency and overactivation of CFTR may cause fluid and salt secretion related diseases. The aim of this study was to identify natural compounds that are able to stimulate wild-type (wt) and ΔF508 mutant CFTR channel activities in CFTR-expressing Fischer rat thyroid (FRT) cells. We found that dehydrocostuslactone [DHC, (3aS, 6aR, 9aR, 9bS)-decahydro-3,6,9-tris (methylene) azuleno [4,5-b] furan-2(3H)-one)] dose dependently potentiates both wt and ΔF508 mutant CFTR-mediated iodide influx in cell-based fluorescent assays and CFTR-mediated Clâ » currents in short-circuit current studies, and the activations could be reversed by the CFTR inhibitor CFTRinh-172. Maximal CFTR-mediated apical Clâ » current secretion in CFTR-expressing FRT cells was stimulated by 100 µM DHC. Determination of intracellular cAMP content showed that DHC modestly but significantly increased cAMP level in FRT cells, but cAMP elevation effects contributed little to DHC-stimulated iodide influx. DHC also stimulated CFTR-mediated apical Clâ » current secretion in FRT cells expressing ΔF508-CFTR. Subsequent studies demonstrated that activation of CFTR by DHC is forskolin dependent. DHC represents a new class of CFTR potentiators that may have therapeutic potential in CFTR-related diseases.
Description Country affiliation: China
Author Affiliation: Wang X ( a School of life sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University , Dalian , 116081 , China.)
ISSN 10286020
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2013-01-01
Publisher Place Great Britain (UK)
e-ISSN 14772213
Journal Journal of Asian Natural Products Research
Volume Number 15
Issue Number 8

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Source: WHO-Global Index Medicus