期刊
FRONTIERS IN PHARMACOLOGY
卷 3, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2012.00176
关键词
cystic fibrosis; CFTR; trafficking; quabain; microarray; connectivity map; hierarchical clustering; CFBE cells
资金
- CIHR
- Canadian Cystic Fibrosis Foundation
- Pasteur Institute-Fondazione Cenci Bolognetti
- prof. Di Mauro E. research fellowship at the Biology and Biotechnology Charles Darwin, BBCD department, Sapienza University, Rome, Italy
- Canadian Institutes of Health Research CIHR [CPG-95270, IR0-97568]
- Fondazione Telethon Funding Source: Custom
Most cases of cystic fibrosis (CF) are caused by the deletion of a single phenylalanine residue at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutant F508del-CFTR is retained in the endoplasmic reticulum and degraded, but can be induced by low temperature incubation (29 degrees C) to traffic to the plasma membrane where it functions as a chloride channel. Here we show that, cardiac glycosides, at nanomolar concentrations, can partially correct the trafficking of F508del-CFTR in human CF bronchial epithelial cells (CFBE41o-) and in an F508del-CFTR mouse model. Comparison of the transcriptional profiles obtained with polarized CFBE41o-cells after treatment with ouabain and by low temperature has revealed a striking similarity between the two corrector treatments that is not shared with other correctors. In summary, our study shows a novel function of ouabain and its analogs in the regulation of F508del-CFTR trafficking and suggests that compounds that mimic this low temperature correction of trafficking will provide new avenues for the development of therapeutics for CF.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据