Mutant cystic fibrosis transmembrane conductance regulator inhibits acidification and apoptosis in C127 cells: Possible relevance to cystic fibrosis

摘要

We have shown elsewhere that acidification is an early event in apoptosis, preceding DNA cleavage. Cells expressing the most common mutation (delF508) of the cystic fibrosis transmembrane regulator (CFTR) exhibit a higher resting intracellular pH and are unable to secrete chloride and bicarbonate in response to cAMP. We hypothesized that defective acidification in cells expressing delF508 CFTR would interfere with the acidification that accompanies apoptosis, which, in turn, would prevent endonuclease activation and cleavage of DNA.