Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the α-glucosidase inhibitor miglustat
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- 作者：Caroline Norez ; Sabrina Noel ; Martina Wilke ; Marcel Bijvelds ; Huub Jorna ; Patricia Melin ; Hugo DeJonge and Frederic Becq
- 关键词：Cystic fibrosis transmembrane conductance regulator ; Miglustat ; Castanospermine ; Calnexin ; Chloride channels ; delF508-mice
- 刊名：FEBS Letters
- 出版年：2006
- 出版时间：3 April 2006
- 年：2006
- 卷：580
- 期：8
- 页码：2081-2086
- 全文大小：805 K
文摘
In the disease cystic fibrosis (CF), the most common mutation delF508 results in endoplasmic reticulum retention of misfolded CF gene proteins (CFTR). We show that the α-1,2-glucosidase inhibitor miglustat (N-butyldeoxynojirimycin, NB-DNJ) prevents delF508-CFTR/calnexin interaction and restores cAMP-activated chloride current in epithelial CF cells. Moreover, miglustat rescues a mature and functional delF508-CFTR in the intestinal crypts of ileal mucosa from delF508 mice. Since miglustat is an orally active orphan drug (Zavesca®) prescribed for the treatment of Gaucher disease, our findings provide the basis for future clinical evaluation of miglustat in CF patients.