Source:http://linkedlifedata.com/resource/pubmed/id/12581736
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2003-2-12
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pubmed:abstractText |
Excess ER stress induces caspase-12 activation and/or cytochrome c release, causing caspase-9 activation. Little is known about their relationship during ER stress-mediated cell death. Upon ER stress, P19 embryonal carcinoma (EC) cells showed activation of various caspases, including caspase-3, caspase-8, caspase-9, and caspase-12, and extensive DNA fragmentation. We examined the relationship between ER stress-mediated cytochrome c/caspase-9 and caspase-12 activation by using caspase-9- and caspase-8-deficient mouse embryonic fibroblasts and a P19 EC cell clone [P19-36/12 (-) cells] lacking expression of caspase-12. Caspase-9 and caspase-8 deficiency inhibited and delayed the onset of DNA fragmentation but did not inhibit caspase-12 processing induced by ER stress. P19-36/12 (-) cells underwent apoptosis upon ER stress, with cytochrome c release and caspase-8 and caspase-9 activation. The dominant negative form of FADD and z-VAD-fmk inhibited caspase-8, caspase-9, Bid processing, cytochrome c release, and DNA fragmentation induced by ER stress, suggesting that caspase-8 and caspase-9 are the main caspases involved in ER stress-mediated apoptosis of P19-36/12 (-) cells. Caspase-8 deficiency also inhibited the cytochrome c release induced by ER stress. Thus, in parallel with the caspase-12 activation, ER stress triggers caspase-8 activation, resulting in cytochrome c/caspase-9 activation via Bid processing.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp12 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 12,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2003 Elsevier Science (USA)
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
156-66
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12581736-Animals,
pubmed-meshheading:12581736-Apoptosis,
pubmed-meshheading:12581736-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:12581736-Carrier Proteins,
pubmed-meshheading:12581736-Caspase 12,
pubmed-meshheading:12581736-Caspase 8,
pubmed-meshheading:12581736-Caspase 9,
pubmed-meshheading:12581736-Caspases,
pubmed-meshheading:12581736-Cytochrome c Group,
pubmed-meshheading:12581736-DNA Fragmentation,
pubmed-meshheading:12581736-Endoplasmic Reticulum,
pubmed-meshheading:12581736-Enzyme Activation,
pubmed-meshheading:12581736-Immunologic Techniques,
pubmed-meshheading:12581736-Mice,
pubmed-meshheading:12581736-Protein Processing, Post-Translational,
pubmed-meshheading:12581736-Signal Transduction,
pubmed-meshheading:12581736-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation.
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pubmed:affiliation |
Division of Development, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-machi, Kodaira, Tokyo 187-8502, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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