ACELL October 46/4
نویسندگان
چکیده
Illek, Beate, Lei Zhang, Nancy C. Lewis, Richard B. Moss, Jian-Yun Dong, and Horst Fischer. Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am. J. Physiol. 277 (Cell Physiol. 46): C833–C839, 1999.—The patch-clamp technique was used to investigate the effects of the isoflavone genistein on disease-causing mutations (G551D and DF508) of the cystic fibrosis transmembrane conductance regulator (CFTR). In HeLa cells recombinantly expressing the trafficking-competent G551D-CFTR, the forskolin-stimulated Cl currents were small, and average open probability of G551D-CFTR was Po 5 0.047 6 0.019. Addition of genistein activated Cl currents ,10-fold, and the Po of G551D-CFTR increased to 0.49 6 0.12, which is a Po similar to wild-type CFTR. In cystic fibrosis (CF) epithelial cells homozygous for the traffickingimpaired DF508 mutation, forskolin and genistein activated Cl currents only after 4-phenylbutyrate treatment. These data suggested that genistein activated CFTR mutants that were present in the cell membrane. Therefore, we tested the effects of genistein in CF patients with the G551D mutation in nasal potential difference (PD) measurements in vivo. The perfusion of the nasal mucosa of G551D CF patients with isoproterenol had no effect; however, genistein stimulated Cl-dependent nasal PD by, on average, 22.4 6 0.6 mV, which corresponds to 16.9% of the responses (to b-adrenergic stimulation) found in healthy subjects.
منابع مشابه
ACELL October 46/4
NABENDU S. CHATTERJEE,1 CHANDIRA K. KUMAR,1 ALVARO ORTIZ,1 STANLEY A. RUBIN,2 AND HAMID M. SAID1 1Medical Research Service, Veterans Affairs Medical Center, Long Beach 90822, and Department of Medicine and Physiology/Biophysics, University of California School of Medicine, Irvine 92697; and 2Veterans Affairs West Los Angeles, Los Angeles 90073, and Department of Medicine, University of Californ...
متن کاملACELL October 46/4
Bahar, Sonya, Christopher T. Gunter, Cheryl Wu, Scott D. Kennedy, and Philip A. Knauf. Persistence of external chloride and DIDS binding after chemical modification of Glu-681 in human band 3. Am. J. Physiol. 277 (Cell Physiol. 46): C791–C799, 1999.—Although its primary function is monovalent anion exchange, the band 3 protein also cotransports divalent anions together with protons at low pH. T...
متن کاملACELL October 46/4
Parfenova, Helena, John Haffner, and Charles W. Leffler. Phosphorylation-dependent stimulation of prostanoid synthesis by nigericin in cerebral endothelial cells. Am. J. Physiol. 277 (Cell Physiol. 46): C728–C738, 1999.— Nigericin decreases intracellular pH (pHi) and stimulates prostanoid (PG) synthesis in endothelial cells from cerebral microvessels of newborn pigs. Nigericin-induced PG produc...
متن کاملACELL November 46/5
ESTHER TITOS,1 NAN CHIANG,2 CHARLES N. SERHAN,2 MARIO ROMANO,3 JOAN GAYA,4 GLORIA PUEYO,5 AND JOAN CLÀRIA1 1DNA Unit and 4Hormonal Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clı́nic and 5Quı́mica Farmacéutica Bayer (Consumer Care Division), Barcelona 08036, Spain; 2Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Periop...
متن کامل