| Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis. | |
| | |
MedLine Citation:
|
PMID: 16738803 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Matthieu Sourdeval; Christophe Lemaire; Aurélien Deniaud; Laurent Taysse; Sébastien Daulon; Patrick Breton; Catherine Brenner; Emmanuelle Boisvieux-Ulrich; Francelyne Marano |
Related Documents
:
|
19020723 - Evaluation of cytotoxic effects induced by bcl-2 and bcl-xl antisense-oligodeoxynucleot... 15026553 - Down-regulation of bcl-2 is associated with cisplatin resistance in human small cell lu... 1358293 - P-glycoprotein-mediated multidrug resistance and cytotoxic effector cells. |
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 |
Affiliation:
|
Labortoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris 7-Denis Diderot, case 70-73, 2 place Jussieu, 75251 Paris Cedex 05, France. msourdeval@paris7.jussieu.fr |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis / drug effects* Azoles / pharmacology Caspases / metabolism* Cell Adhesion / drug effects Cell Membrane Permeability* / drug effects, physiology Cells, Cultured Cyclosporine / pharmacology Hela Cells Humans Mechlorethamine / toxicity Melatonin / pharmacology Mice 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 |
| Chemical | |
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
Previous Document: Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loadin...
Next Document: General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain.