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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2003-12-3
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pubmed:abstractText |
Signalling through the death receptor CD95 induces apoptosis by formation of a signalling complex at the cell membrane and subsequent caspase-8 and caspase-3-activation. Treatment of Jurkat T cells with protonophores across the mitochondrial membrane such as 2,4-dinitrophenol (DNP) enhances the death-inducing capacity of CD95. In this study, we show that this enhancement is due to the specific acceleration of caspase-8-processing and activation at the CD95-receptor. DNP-treatment did not affect NF-kappaB-induction by CD95. Immunoprecipitation experiments showed that the amounts of the adapter FADD/MORT1 and pro-caspase-8 at the CD95-receptor were not altered by DNP. Subcellular fractionation studies revealed that the amount of mature caspase-8 but not pro-caspase at the membrane was increased following CD95-stimulation in the presence of DNP. As a consequence of caspase-activation, c-FLIP-levels in the cytosol decreased. In Jurkat cells overexpressing c-FLIPS, DNP was still able to enhance caspase-activation. The enhancing capacity of DNP was seen in some cell lines (Jurkat, CEM and HeLa) but not in SKW6 cells and was also found in mitogen-stimulated human T cells. Furthermore, the enhancement extended to TRAIL-induced caspase-activation. Thus, a mechanism exists by which caspase-8-activation can be accelerated at death receptors and this mechanism can be triggered by targeting mitochondrial oxidative phosphorylation.
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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/2,4-Dinitrophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carbonyl Cyanide m-Chlorophenyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Uncoupling Agents
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0161-5890
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
661-70
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14644092-2,4-Dinitrophenol,
pubmed-meshheading:14644092-Antigens, CD95,
pubmed-meshheading:14644092-Apoptosis,
pubmed-meshheading:14644092-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:14644092-Carbonyl Cyanide m-Chlorophenyl Hydrazone,
pubmed-meshheading:14644092-Carrier Proteins,
pubmed-meshheading:14644092-Caspase 8,
pubmed-meshheading:14644092-Caspases,
pubmed-meshheading:14644092-Cell Line,
pubmed-meshheading:14644092-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:14644092-Enzyme Activation,
pubmed-meshheading:14644092-HeLa Cells,
pubmed-meshheading:14644092-Humans,
pubmed-meshheading:14644092-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14644092-Jurkat Cells,
pubmed-meshheading:14644092-Lymphocyte Activation,
pubmed-meshheading:14644092-Mitochondria,
pubmed-meshheading:14644092-Oxidative Phosphorylation,
pubmed-meshheading:14644092-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:14644092-Signal Transduction,
pubmed-meshheading:14644092-T-Lymphocytes,
pubmed-meshheading:14644092-Uncoupling Agents
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pubmed:year |
2004
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pubmed:articleTitle |
Enhancement of death-receptor induced caspase-8-activation in the death-inducing signalling complex by uncoupling of oxidative phosphorylation.
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pubmed:affiliation |
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstrasse 9, D-81675 Munich, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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