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Rescue of functional delF508‐CFTR channels in cystic fibrosis epithelial cells by the α‐glucosidase inhibitor miglustat
Author(s) -
Norez Caroline,
Noel Sabrina,
Wilke Martina,
Bijvelds Marcel,
Jorna Huub,
Melin Patricia,
DeJonge Hugo,
Becq Frederic
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.03.010
Subject(s) - cystic fibrosis , endoplasmic reticulum , chloride channel , calnexin , cystic fibrosis transmembrane conductance regulator , pharmacology , er retention , medicine , biology , chemistry , microbiology and biotechnology , gene , biochemistry , calreticulin , mutant
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.