2007-09-05
Cholesterol depletion and genistein as tools to promote F508delCFTR retention at the plasma membrane
Publication
Publication
Cellular Physiology and Biochemistry , Volume 20 - Issue 5 p. 473- 482
Background/aims: F508delCFTR-, but not wtCFTR-, expressing fibroblasts resemble Niemann Pick type C cells in the massive intracellular accumulation of free cholesterol. The recruitment and activation of F508delCFTR by cholesterol depletion was studied. Methods: Filipin staining, forskolin-stimulated anion efflux and FITC-dextran uptake were studied in control cells and fibroblasts treated with 2-hydroxypropyl β-cyclodextrin phosphatidylcholine large unilamellar vesicles to deplete cellular free cholesterol.Results: Treatment of F508delCFTR-, but not wtCFTR-, expressing fibroblasts with 2-hydroxypropyl β-cyclodextrin resulted in a reduction in cellular cholesterol and a potentiation of the forskolin-induced anion efflux. In addition, forskolin also promoted a massive increase in the rate of endocytosis in F508delCFTR fibroblasts, which was absent in genistein- or cyclodextrin-treated cultures.Conclusion: The results not only suggest that reducing cellular cholesterol may serve as pharmacotherapeutic tool in the treatment of cystic fibrosis but also reveal a novel mechanism for genistein regulation of F508delCFTR, i.e. retention by inhibition of endocytosis. Copyright
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doi.org/10.1159/000107531, hdl.handle.net/1765/36585 | |
Cellular Physiology and Biochemistry | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
Lim, C., Bijvelds, M., Nigg, A., Schoonderwoerd, K., Houtsmuller, A., de Jonge, H., & Tilly, B. (2007). Cholesterol depletion and genistein as tools to promote F508delCFTR retention at the plasma membrane. Cellular Physiology and Biochemistry, 20(5), 473–482. doi:10.1159/000107531 |