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• W1973254311 endingPage "206" @default.
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• W1973254311 abstract "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." @default.
• W1973254311 created "2016-06-24" @default.
• W1973254311 creator A5010768681 @default.
• W1973254311 creator A5063813825 @default.
• W1973254311 date "2000-02-01" @default.
• W1973254311 modified "2023-09-25" @default.
• W1973254311 title "Cytochrome c Release from Mitochondria of Early Postimplantation Murine Embryos Exposed to 4-Hydroperoxycyclophosphamide, Heat Shock, and Staurosporine" @default.
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• W1973254311 doi "https://doi.org/10.1006/taap.1999.8849" @default.
• W1973254311 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10652248" @default.
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