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J. Biol. Chem., Vol. 280, Issue 7, 5221-5226, February 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/7/5221    most recent M412972200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berger, A. L. Articles by Welsh, M. J. Search for Related Content PubMed PubMed Citation Articles by Berger, A. L. Articles by Welsh, M. J. Social Bookmarking                      What's this?

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¶

From the Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242

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-F508. 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 F508 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.

Received for publication, November 16, 2004

^* This work was supported by NHLBI, National Institutes of Health Grants HL29851 and HL61234 and Cystic Fibrosis Foundation Grant R458-CR02. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

Supported by National Institutes of Health Grant DK062938.

^¶ Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Howard Hughes Medical Institute, 500 EMRB, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. Tel.: 319-335-7619; Fax: 319-335-7623; E-mail: michael-welsh{at}uiowa.edu.

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