title: The calpain, caspase 12, caspase 3 cascade leading to apoptosis is altered in F508del-CFTR expressing cells.
abstract: In cystic fibrosis (CF), the most frequent mutant variant of the cystic fibrosis transmembrane conductance regulator (CFTR), F508del-CFTR protein, is misfolded and retained in the endoplasmic reticulum (ER). We previously showed that the unfolded protein response (UPR) may be triggered in CF. Since prolonged UPR activation leads to apoptosis via the calcium-calpain-caspase-12-caspase-3 cascade and because apoptosis is altered in CF, our aim was to compare the ER stress-induced apoptosis pathway between wild type (Wt) and F508del-CFTR expressing cells. Here we show that the calcium-calpain-caspase-12-caspase-3 cascade is altered in F508del-CFTR expressing cells. We propose that this alteration is involved in the altered apoptosis triggering observed in CF.
authors.affiliation: Inserm, Brest, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kerbiriou
authors.forename: Ling
authors.initials: L
authors.lastname: Teng
authors.forename: Nathalie
authors.initials: N
authors.lastname: Benz
authors.forename: Pascal
authors.initials: P
authors.lastname: Trouvé
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002154:Calpain / Q000378:metabolism*; D053454:Caspase 12 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019284:Thapsigargin; D002154:Calpain; D053454:Caspase 12; D053148:Caspase 3; C484806:CAPN1 protein, human; C569870:CAPN2 protein, human