| Activation of caspase-9, but not caspase-2 or caspase-8, is essential for heat-induced apoptosis in Jurkat cells. | |
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MedLine Citation:
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PMID: 20978129 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Exposure of cells to hyperthermia is known to induce apoptosis, although the underlying mechanisms are only partially understood. Here, we examine the molecular requirements necessary for heat-induced apoptosis using genetically modified Jurkat T-lymphocytes. Cells stably overexpressing Bcl-2/Bcl-x(L) or stably depleted of Apaf-1 were completely resistant to heat-induced apoptosis, implicating the involvement of the mitochondria-mediated pathway. Pretreatment of wild-type cells with the cell-permeable biotinylated general caspase inhibitor b-VAD-fmk (biotin-Val-Ala-Asp(OMe)-CH(2)F) both inhibited heat-induced apoptosis and affinity-labeled activated initiator caspase-2, -8, and -9. Despite this finding, however, cells engineered to be deficient in caspase-8, caspase-2, or the caspase-2 adaptor protein RAIDD (receptor-interacting protein (RIP)-associated Ich-1/CED homologous protein with death domain) remained susceptible to heat-induced apoptosis. Additionally, b-VAD-fmk failed to label any activated initiator caspase in Apaf-1-deficient cells exposed to hyperthermia. Cells lacking Apaf-1 or the pro-apoptotic BH3-only protein Bid exhibited lower levels of heat-induced Bak activation, cytochrome c release, and loss of mitochondrial membrane potential, although cleavage of Bid to truncated Bid (tBid) occurred downstream of caspase-9 activation. Combined, the data suggest that caspase-9 is the critical initiator caspase activated during heat-induced apoptosis and that tBid may function to promote cytochrome c release during this process as part of a feed-forward amplification loop. |
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Authors:
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Shary N Shelton; Cindy D Dillard; John D Robertson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-26 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-20 Completed Date: 2011-01-24 Revised Date: 2011-12-26 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 40525-33 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects,
physiology* Apoptotic Protease-Activating Factor 1 / genetics, metabolism BH3 Interacting Domain Death Agonist Protein / genetics, metabolism CRADD Signaling Adaptor Protein / genetics, metabolism Caspase 2 / antagonists & inhibitors, genetics, metabolism* Caspase 8 / antagonists & inhibitors, genetics, metabolism* Caspase 9 / antagonists & inhibitors, genetics, metabolism* Cysteine Endopeptidases / genetics, metabolism* Enzyme Activation / drug effects, physiology Heat-Shock Response / drug effects, physiology* Humans Jurkat Cells Protease Inhibitors / pharmacology bcl-X Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K22 ES011647/ES/NIEHS NIH HHS; P20 RR016443/RR/NCRR NIH HHS; P20 RR016475/RR/NCRR NIH HHS; T32 ES007079/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/APAF1 protein, human; 0/Apoptotic Protease-Activating Factor 1; 0/BCL2L1 protein, human; 0/BH3 Interacting Domain Death Agonist Protein; 0/BID protein, human; 0/CRADD Signaling Adaptor Protein; 0/CRADD protein, human; 0/Protease Inhibitors; 0/bcl-X Protein; EC 3.4.22.-/CASP2 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Cysteine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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