Document Detail

CFTR modulates programmed cell death by decreasing intracellular pH in Chinese hamster lung fibroblasts.
MedLine Citation:
PMID:  11502558     Owner:  NLM     Status:  MEDLINE    
To study the potential influence of cystic fibrosis conductance regulator (CFTR) on intracellular pH regulation during apoptosis induction, we used PS120 Chinese hamster lung fibroblasts devoid of the Na(+)/H(+) exchanger (NHE1 isoform) transfected with constructs, allowing the expression of CFTR and/or NHE1. Kinetics of lovastatin-induced apoptosis were measured by orcein staining, double staining with Hoechst-33258, propidium iodide, DNA fragmentation, and annexin V labeling. In PS120 control cells, the percentage of apoptotic cells after 40 h of lovastatin treatment was 23 +/- 3%, whereas in PS120 CFTR-transfected cells, this percentage was 40 +/- 4%. In PS120 NHE1 cells, the transfection with CFTR did not modify the percentage of apoptotic cells after 40 h (control: 19 +/- 3%, n = 8; CFTR: 17 +/- 1%, n = 8), indicating that blocking intracellular acidification by overexpressing the Na(+)/H(+) exchanger inhibited the enhancement of apoptosis induced by CFTR. In all cell lines, the initial pH values were identical (pH = 7.46 +/- 0.04, n = 9), and treatment with lovastatin led to intracellular acidification. However, the pH value after 40 h was lower in PS120 CFTR-transfected cells (pH = 6.85 +/- 0.02, n = 10) than in PS120 cells (pH = 7.15 +/- 0.03, n = 10). To further investigate the origin of this increased intracellular acidification observed in CFTR-transfected cells, the activity of the DIDS-inhibitable Cl(-)/HCO exchanger was studied. 8-Bromoadenosine 3',5'-cyclic monophosphate incubation resulted in Cl(-)/HCO exchanger activation in PS120 CFTR-transfected cells but had no effect on PS120 cells. Together, our results suggest that CFTR can enhance apoptosis in Chinese hamster lung fibroblasts, probably due to the modulation of the Cl(-)/HCO exchanger, resulting in a more efficient intracellular acidification.
H Barrière; C Poujeol; M Tauc; J M Blasi; L Counillon; P Poujeol
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  281     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-14     Completed Date:  2001-09-13     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C810-24     Citation Subset:  IM    
Unité Mixte de Recherche-Centre National de la Recherche Scientifique 6548, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2, France.
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MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Angiogenesis Inhibitors / pharmacology
Apoptosis / drug effects,  physiology*
Cell Line
Chloride Channels / drug effects,  physiology
Chlorides / metabolism
Cystic Fibrosis Transmembrane Conductance Regulator / drug effects,  genetics,  physiology*
DNA Fragmentation
Gluconates / pharmacology
Hydrogen-Ion Concentration*
Iodides / pharmacology
Lovastatin / pharmacology
Nitrobenzoates / pharmacology
Recombinant Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Hydrogen Antiporter / genetics,  physiology*
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Chloride Channels; 0/Chlorides; 0/Gluconates; 0/Iodides; 0/Nitrobenzoates; 0/Recombinant Proteins; 0/Sodium-Hydrogen Antiporter; 0/growth factor-activatable Na-H exchanger NHE-1; 107254-86-4/5-nitro-2-(3-phenylpropylamino)benzoic acid; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 526-95-4/gluconic acid; 75330-75-5/Lovastatin

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