ABCMdb

PMID: 11786964

Zsembery A, Jessner W, Sitter G, Spirli C, Strazzabosco M, Graf J
Correction of CFTR malfunction and stimulation of Ca-activated Cl channels restore HCO3- secretion in cystic fibrosis bile ductular cells.
Hepatology. 2002 Jan;35(1):95-104., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Gly542* Human cholangiocytes were isolated from control livers and from 1 patient with CF (⌬F508/G542X mutations). Login to comment 7 ABCC7 p.Gly542* Consistent with reports that premature stop codon mutations (class I; e.g., G542X) can be read over by treatment with aminoglycoside antibiotics, exposure of CF cholangiocytes to gentamicin restored activation by cAMP of Cl- current and HCO3 - secretion. Login to comment 26 ABCC7 p.Gly542* In addition, the CF cells available to us were heterozygous at the CFTR locus, carrying the ⌬F508 trafficking mutation (class II23) on one allele and the G542X premature stop codon mutation (class I23) on the other. Login to comment 139 ABCC7 p.Gly542* Note: (1) Absence of effect of raising intracellular cAMP (column 2) and of the continuous presence of extracellular ATP (column 3); (2) large activation of HCO3 - extrusion by raising intracellular Ca2ϩ concentration with ionomycin (column 4); and (3) unveiling of cAMP-stimulated HCO3 - secretion by restoring translation of CFTR-G542X with gentamycin (column 5). Login to comment 155 ABCC7 p.Gly542* This current stimulation was transient and current returned towards control values within 1 minute (data not shown).22,39 Correction of Cl- and HCO3 - Secretory Defect in CFhBDC by Gentamicin Class I mutations of CFTR, which result in premature stop codons (e.g., G542X) can be corrected with certain aminoglycoside antibiotics.24-26 We pretreated CFhBDC with 200 ␮g/mL gentamicin for 18 hours and measured HCO3 - extrusion in the presence of cAMPmix. Login to comment 173 ABCC7 p.Gly542* Thus, activation by cAMP of Cl- currents and HCO3 - secretion could both be restored in CF cholangiocytes carrying the premature stop codon mutation (G542X). Login to comment 215 ABCC7 p.Gly542* The CFTR-deficient cells used in this study were heterozygous exhibiting the ⌬F508/G542X alleles, mutations belonging to class II and class I groups, respectively. Login to comment 219 ABCC7 p.Gly542* We had previously shown that chaperoning with glycerol leads to proper surface membrane targeting of CFTR-⌬F508, which restored cAMP-dependent HCO3 - transport in CF pancreatic ductular cells.9 Unfortunately, no more ⌬F508/G542X cholangiocytes were available and analogous experiments to restore CFTR function in bile ductular cells could not be performed. Login to comment