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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
1999-11-18
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pubmed:abstractText |
We have previously shown that the small heat shock protein HSP27 inhibited apoptotic pathways triggered by a variety of stimuli in mammalian cells. The present study demonstrates that HSP27 overexpression decreases U937 human leukemic cell sensitivity to etoposide-induced cytotoxicity by preventing apoptosis. As observed for Bcl-2, HSP27 overexpression delays poly(ADP-ribose)polymerase cleavage and procaspase-3 activation. In contrast with Bcl-2, HSP27 overexpression does not prevent etoposide-induced cytochrome c release from the mitochondria. In a cell-free system, addition of cytochrome c and dATP to cytosolic extracts from untreated cells induces the proteolytic activation of procaspase-3 in both control and bcl-2-transfected U937 cells but fails to activate procaspase-3 in HSP27-overexpressing cells. Immunodepletion of HSP27 from cytosolic extracts increases cytochrome c/dATP-mediated activation of procaspase-3. Overexpression of HSP27 also prevents procaspase-9 activation. In the cell-free system, immunodepletion of HSP27 increases LEDH-AFC peptide cleavage activity triggered by cytochrome c/dATP treatment. We conclude that HSP27 inhibits etoposide-induced apoptosis by preventing cytochrome c and dATP-triggered activity of caspase-9, downstream of cytochrome c release.
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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'-deoxyadenosine triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0892-6638
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2061-70
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10544189-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:10544189-Apoptosis,
pubmed-meshheading:10544189-Caspase 3,
pubmed-meshheading:10544189-Caspase 9,
pubmed-meshheading:10544189-Caspases,
pubmed-meshheading:10544189-Cytochrome c Group,
pubmed-meshheading:10544189-Deoxyadenine Nucleotides,
pubmed-meshheading:10544189-Drug Resistance, Neoplasm,
pubmed-meshheading:10544189-Enzyme Activation,
pubmed-meshheading:10544189-Enzyme Precursors,
pubmed-meshheading:10544189-Etoposide,
pubmed-meshheading:10544189-Heat-Shock Proteins,
pubmed-meshheading:10544189-Humans,
pubmed-meshheading:10544189-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10544189-U937 Cells
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pubmed:year |
1999
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pubmed:articleTitle |
HSP27 inhibits cytochrome c-dependent activation of procaspase-9.
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pubmed:affiliation |
INSERM U517, Groupe Biologie et Thérapie des Cancers (JE 515), Faculty of Medicine and Pharmacy, 21033 Dijon, France. cgarrido@u-bourgogne.fr
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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