Document Detail

Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis.
MedLine Citation:
PMID:  16738803     Owner:  NLM     Status:  MEDLINE    
In the present study, the toxicity of yperite, SM, and its structural analogue mechlorethamine, HN2, was investigated in a human bronchial epithelial cell line 16HBE. Cell detachment was initiated by caspase-2 activation, down-regulation of Bcl-2 and loss of mitochondrial membrane potential. Only in detached cells, mustards induced apoptosis associated with increase in p53 expression, Bax activation, decrease in Bcl-2 expression, opening of the mitochondrial permeability transition pore, release of cytochrome c, caspase-2, -3, -8, -9 and -13 activation and DNA fragmentation. Apoptosis, occurring only in detached cells, could be recognized as anoikis and the mitochondrion, involved both in cell detachment and subsequent cell death, appears to be a crucial checkpoint. Based on our understanding of the apoptotic pathway triggered by mustards, we demonstrated that inhibition of the mitochondrial pathway by ebselen, melatonin and cyclosporine A markedly prevented mustard-induced anoikis, pointing to these drugs as interesting candidates for the treatment of mustard-induced airway epithelial lesions.
Matthieu Sourdeval; Christophe Lemaire; Aurélien Deniaud; Laurent Taysse; Sébastien Daulon; Patrick Breton; Catherine Brenner; Emmanuelle Boisvieux-Ulrich; Francelyne Marano
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  11     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-20     Completed Date:  2006-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1545-59     Citation Subset:  IM    
Labortoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris 7-Denis Diderot, case 70-73, 2 place Jussieu, 75251 Paris Cedex 05, France.
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MeSH Terms
Apoptosis / drug effects*
Azoles / pharmacology
Caspases / metabolism*
Cell Adhesion / drug effects
Cell Membrane Permeability* / drug effects,  physiology
Cells, Cultured
Cyclosporine / pharmacology
Hela Cells
Mechlorethamine / toxicity
Melatonin / pharmacology
Mitochondria / metabolism*
Models, Biological
Multiprotein Complexes / metabolism
Mustard Gas / toxicity*
Organoselenium Compounds / pharmacology
Proto-Oncogene Proteins c-bcl-2 / physiology
Respiratory Mucosa / drug effects*,  metabolism
Tumor Suppressor Protein p53 / physiology
Reg. No./Substance:
0/Azoles; 0/Multiprotein Complexes; 0/Organoselenium Compounds; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 505-60-2/Mustard Gas; 51-75-2/Mechlorethamine; 59865-13-3/Cyclosporine; 60940-34-3/ebselen; 73-31-4/Melatonin; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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