Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity

Allan L Berger; Christoph O Randak; Lynda S Ostedgaard; Philip H Karp; Daniel W Vermeer; Michael J Welsh

doi:10.1074/jbc.M412972200

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Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity

Journal article

Open access

Peer reviewed

Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity

Allan L Berger, Christoph O Randak, Lynda S Ostedgaard, Philip H Karp, Daniel W Vermeer and Michael J Welsh

The Journal of biological chemistry, Vol.280(7), pp.5221-5226

02/18/2005

DOI: 10.1074/jbc.M412972200

PMID: 15582996

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Abstract

Compounds that enhance either the function or biosynthetic processing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel may be of value in developing new treatments for cystic fibrosis (CF). Previous studies suggested that the herbal extract curcumin might affect the processing of a common CF mutant, CFTR-DeltaF508. Here, we tested the hypothesis that curcumin influences channel function. Curcumin increased CFTR channel activity in excised, inside-out membrane patches by reducing channel closed time and prolonging the time channels remained open. Stimulation was dose-dependent, reversible, and greater than that observed with genistein, another compound that stimulates CFTR. Curcumin-dependent stimulation required phosphorylated channels and the presence of ATP. We found that curcumin increased the activity of both wild-type and DeltaF508 channels. Adding curcumin also increased Cl(-) transport in differentiated non-CF airway epithelia but not in CF epithelia. These results suggest that curcumin may directly stimulate CFTR Cl(-) channels.

Cyclic AMP-Dependent Protein Kinases - metabolism

Epithelial Cells - metabolism

Epithelial Cells - drug effects

Humans

Curcumin - pharmacology

Cystic Fibrosis Transmembrane Conductance Regulator - agonists

Cystic Fibrosis Transmembrane Conductance Regulator - metabolism

Bronchi - drug effects

Dose-Response Relationship, Drug

Animals

Chlorides - metabolism

Genistein - pharmacology

Cystic Fibrosis Transmembrane Conductance Regulator - genetics

Cell Membrane - metabolism

Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors

Phosphorylation - drug effects

COS Cells

Ion Channel Gating - drug effects

Sequence Deletion - genetics

Details

Title: Subtitle: Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity
Creators: Allan L Berger - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Christoph O Randak
Lynda S Ostedgaard
Philip H Karp
Daniel W Vermeer
Michael J Welsh
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(7), pp.5221-5226
DOI: 10.1074/jbc.M412972200
PMID: 15582996
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL29851 / NHLBI NIH HHS HL61234 / NHLBI NIH HHS DK062938 / NIDDK NIH HHS
Language: English
Date published: 02/18/2005
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Neurosurgery; Internal Medicine
Record Identifier: 9984020759302771

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