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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-9-8
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pubmed:abstractText |
Exposure to bleomycin in rodents induces lung injury and fibrosis. Alveolar epithelial cell death has been hypothesized as an initiating mechanism underlying bleomycin-induced lung injury and fibrosis. In the present study we evaluated the contribution of mitochondrial and receptor-meditated death pathways in bleomycin-induced death of mouse alveolar epithelial cells (MLE-12 cells) and primary rat alveolar type II cells. Control MLE-12 cells and primary rat alveolar type II cells died after 48 h of exposure to bleomycin. Both MLE-12 cells and rat alveolar type II cells overexpressing Bcl-X(L) did not undergo cell death in response to bleomycin. Dominant negative Fas-associating protein with a death domain failed to prevent bleomycin-induced cell death in MLE-12 cells. Caspase-8 inhibitor CrmA did not prevent bleomycin-induced cell death in primary rat alveolar type II cells. Furthermore, fibroblast cells deficient in Bax and Bak, but not Bid, were resistant to bleomycin-induced cell death. To determine whether the stress kinase JNK was an upstream regulator of Bax activation, MLE-12 cells were exposed to bleomycin in the presence of an adenovirus encoding a dominant negative JNK. Bleomycin-induced Bax activation was prevented by the expression of a dominant negative JNK in MLE-12 cells. Dominant negative JNK prevented cell death in MLE-12 cells and in primary rat alveolar type II cells exposed to bleomycin. These data indicate that bleomycin induces cell death through a JNK-dependent mitochondrial death pathway in alveolar epithelial cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/Bak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bak1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fadd protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fadd protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Fas-Associated Death Domain Protein,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1040-0605
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
289
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
L521-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16148050-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16148050-Animals,
pubmed-meshheading:16148050-Antibiotics, Antineoplastic,
pubmed-meshheading:16148050-Apoptosis,
pubmed-meshheading:16148050-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:16148050-Bleomycin,
pubmed-meshheading:16148050-Carrier Proteins,
pubmed-meshheading:16148050-Cells, Cultured,
pubmed-meshheading:16148050-Fas-Associated Death Domain Protein,
pubmed-meshheading:16148050-Gene Expression,
pubmed-meshheading:16148050-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:16148050-Membrane Proteins,
pubmed-meshheading:16148050-Mice,
pubmed-meshheading:16148050-Mice, Mutant Strains,
pubmed-meshheading:16148050-Mitochondria,
pubmed-meshheading:16148050-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:16148050-Pulmonary Alveoli,
pubmed-meshheading:16148050-Rats,
pubmed-meshheading:16148050-Respiratory Mucosa,
pubmed-meshheading:16148050-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:16148050-bcl-2-Associated X Protein,
pubmed-meshheading:16148050-bcl-X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway.
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pubmed:affiliation |
Div. of Pulmonary & Critical Care, Northwestern University, Chicago, IL 60611, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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