Source:http://linkedlifedata.com/resource/pubmed/id/10652248
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2000-3-10
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| pubmed:abstractText |
Cell death is an early and common event in the pathogenesis associated with the abnormal development induced by a variety of teratogens. Previously, we showed that the cell death induced in day 9 mouse embryos by three teratogens, hyperthermia (HS), 4-hydroperoxycyclophosphamide (4-CP), and sodium arsenite (As), is apoptotic in nature involving the activation of caspase-3, cleavage of poly(ADP-ribose) polymerase (PARP), and DNA fragmentation. We now show that HS, 4-CP, and staurosporine (ST) induce the release of cytochrome c from mitochondria with kinetics suggesting a causal relationship with the activation of caspase-3 and caspase-2. This causal relationship is supported by data showing that procaspase-3 and -2 can be activated in vitro by the addition of cytochrome c to a S-100 fraction prepared from control day 9 embryos. Together, these data support the notion that these three teratogens induce changes in embryonic mitochondria resulting in the release of cytochrome c and the subsequent activation of caspase-9, the upstream activator of caspase-3. Previously, we also showed that cells within the day 9 mouse embryo are differentially sensitive/resistant to the cell death-inducing potential of HS, 4-CP, and As. The most dramatic example of this differential sensitivity is the complete resistance of heart cells, characterized by the lack of caspase-3 activation, PARP cleavage, and DNA fragmentation. We now show that this block in the terminal phase of the apoptotic pathway in heart cells is associated with a lack of teratogen-induced release of cytochrome c. Together, our data indicate that mitochondria play a pivotal role in cell death during the early phases of teratogenesis.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophosphamide,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Teratogens,
http://linkedlifedata.com/resource/pubmed/chemical/perfosfamide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0041-008X
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
162
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
197-206
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10652248-Animals,
pubmed-meshheading:10652248-Apoptosis,
pubmed-meshheading:10652248-Caspases,
pubmed-meshheading:10652248-Culture Techniques,
pubmed-meshheading:10652248-Cyclophosphamide,
pubmed-meshheading:10652248-Cytochrome c Group,
pubmed-meshheading:10652248-DNA Fragmentation,
pubmed-meshheading:10652248-Embryo, Mammalian,
pubmed-meshheading:10652248-Embryo Implantation,
pubmed-meshheading:10652248-Enzyme Activation,
pubmed-meshheading:10652248-Female,
pubmed-meshheading:10652248-Hyperthermia, Induced,
pubmed-meshheading:10652248-Male,
pubmed-meshheading:10652248-Mice,
pubmed-meshheading:10652248-Mitochondria,
pubmed-meshheading:10652248-Myocardium,
pubmed-meshheading:10652248-Pregnancy,
pubmed-meshheading:10652248-Staurosporine,
pubmed-meshheading:10652248-Teratogens
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| pubmed:year |
2000
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| pubmed:articleTitle |
Cytochrome c release from mitochondria of early postimplantation murine embryos exposed to 4-hydroperoxycyclophosphamide, heat shock, and staurosporine.
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| pubmed:affiliation |
Birth Defects Research Laboratory, University of Washington, Seattle, Washington, 98195, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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