Document Detail

Increased oxidative stress induces apoptosis in human cystic fibrosis cells.
MedLine Citation:
PMID:  21931865     Owner:  NLM     Status:  MEDLINE    
Oxidative stress results in deleterious cell function in pathologies associated with inflammation. Here, we investigated the generation of superoxide anion as well as the anti-oxidant defense systems related to the isoforms of superoxide dismutases (SOD) in cystic fibrosis (CF) cells. Pro-apoptotic agents induced apoptosis in CF but not in control cells that was reduced by treatment with SOD mimetic. These effects were associated with increased superoxide anion production, sensitive to the inhibition of IκB-α phosphorylation, in pancreatic but not tracheal CF cells, and reduced upon inhibition of either mitochondrial complex I or NADPH oxidase. CF cells exhibited reduced expression, but not activity, of both Mn-SOD and Cu/Zn-SOD when compared to control cells. Although, expression of EC-SOD was similar in normal and CF cells, its activity was reduced in CF cells. We provide evidence that high levels of oxidative stress are associated with increased apoptosis in CFTR-mutated cells, the sources being different depending on the cell type. These observations underscore a reduced anti-oxidant defense mechanism, at least in part, via diminished EC-SOD activity and regulation of Cu/Zn-SOD and Mn-SOD expressions. These data point to new therapeutic possibilities in targeting anti-oxidant pathways to reduce oxidative stress and apoptosis in CF cells.
Mathilde Rottner; Simon Tual-Chalot; H Ahmed Mostefai; Ramaroson Andriantsitohaina; Jean-Marie Freyssinet; María Carmen Martínez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-12
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-09-20     Completed Date:  2012-02-28     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24880     Citation Subset:  IM    
INSERM, U770, Le Kremlin-Bicêtre, France.
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MeSH Terms
Acetophenones / pharmacology
Allopurinol / pharmacology
Apoptosis / drug effects*
Blotting, Western
Cell Line, Tumor
Cystic Fibrosis / metabolism
Dactinomycin / pharmacology
Electron Spin Resonance Spectroscopy
NADPH Oxidase / metabolism
Oxidative Stress / drug effects*
Superoxide Dismutase / metabolism
Xanthine Oxidase / metabolism
Reg. No./Substance:
0/Acetophenones; 315-30-0/Allopurinol; 50-76-0/Dactinomycin; B6J7B9UDTR/acetovanillone; EC Dismutase; EC Oxidase; EC Oxidase

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