{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T21:19:25Z","timestamp":1771017565475,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":334,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Cystic fibrosis (CF) is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl<jats:sup>\u2212<\/jats:sup> channel. In the search for new CF therapies, small molecules have been identified that rescue the defective channel gating of CF mutants (termed CFTR potentiators). Here, we investigate the long\u2010term effects of genistein, the best\u2010studied CFTR potentiator, on the expression and function of CFTR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>We pre\u2010treated baby hamster kidney (BHK) cells expressing wild\u2010type or F508del\u2010CFTR (the most common CF mutant) with concentrations of genistein that potentiate (30\u2003\u03bcM) or inhibit (100\u2003\u03bcM) CFTR function for 2 or 24\u2003h at 37\u2003\u00b0C before examining CFTR maturation, expression and single\u2010channel activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Using the iodide efflux technique, we found that genistein pre\u2010treatment failed to restore function to F508del\u2010CFTR, but altered that of wild\u2010type CFTR. Pre\u2010treatment of cells with genistein for 2\u2003h had little effect on CFTR processing, whereas pre\u2010treatment for 24\u2003h either augmented (30\u2003\u03bcM genistein) or impaired (100\u2003\u03bcM genistein) CFTR maturation. Using immunocytochemistry, we found that all genistein pre\u2010treatments increased the localization of CFTR protein to the cell surface. However, following the incubation of cells with genistein (100\u2003\u03bcM) for 2\u2003h, individual CFTR Cl<jats:sup>\u2212<\/jats:sup> channels exhibited characteristics of channel block upon channel activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>Genistein pre\u2010treatment alters the maturation, cell surface expression and single\u2010channel function of CFTR in ways distinct from its acute effects. Thus, CFTR potentiators have the potential to influence CFTR by mechanisms distinct from their effects on channel gating.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>153<\/jats:bold>, 1311\u20131323; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707663\">10.1038\/sj.bjp.0707663<\/jats:ext-link>; published online 28 January 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707663","type":"journal-article","created":{"date-parts":[[2008,1,28]],"date-time":"2008-01-28T11:02:04Z","timestamp":1201518124000},"page":"1311-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator"],"prefix":"10.1111","volume":"153","author":[{"given":"A","family":"Schmidt","sequence":"first","affiliation":[]},{"given":"L K","family":"Hughes","sequence":"additional","affiliation":[]},{"given":"Z","family":"Cai","sequence":"additional","affiliation":[]},{"given":"F","family":"Mendes","sequence":"additional","affiliation":[]},{"given":"H","family":"Li","sequence":"additional","affiliation":[]},{"given":"D N","family":"Sheppard","sequence":"additional","affiliation":[]},{"given":"M 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