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• W1680974060 endingPage "3006" @default.
• W1680974060 startingPage "2996" @default.
• W1680974060 abstract "Caspases play a pivotal role in neuronal cell death during development and after trophic factor withdrawal. However, the mechanisms regulating caspase activity and the role played by caspase activation in response to neuronal injury is poorly understood. The tumor suppressor gene p53 has been implicated in the loss of neuronal viability caused by excitotoxic and DNA damaging agents. In the present study we determined if p53-mediated neuronal cell death required caspase activation. DNA damage increased caspase activity in both cultured embryonic telencephalic and postnatal cortical neurons in a p53-dependent manner. Caspase inhibitors protected embryonic telencephalic neurons, but not postnatal cortical neurons, from DNA damage-induced cell death as measured by direct cell counting and annexin V staining. In marked contrast to the caspase inhibitors, an inhibitor of the DNA repair enzyme, poly(ADP-ribose) polymerase, conferred significant protection from genotoxic and excitotoxic cell death on postnatal cortical neurons but had no effect on embryonic neurons. Glutamate-mediated excitotoxicity in postnatal neurons was not associated with measurable changes in caspase activity, consistent with the failure of caspase inhibitors to prevent cell death under these conditions. Moreover, adenovirus-mediated overexpression of p53 killed embryonic and postnatal neurons without activating caspases. Thus, p53-mediated neuronal cell death may occur via both caspase-dependent and caspase-independent pathways. These results demonstrate that p53 is required for caspase activation in response to some forms of neuronal injury. However, the relative importance of caspase activation in neurons depends on the developmental status of the cell and the specific nature of the death stimulus." @default.
• W1680974060 created "2016-06-24" @default.
• W1680974060 creator A5032056146 @default.
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• W1680974060 creator A5080721533 @default.
• W1680974060 creator A5090753844 @default.
• W1680974060 date "1999-04-15" @default.
• W1680974060 modified "2023-10-18" @default.
• W1680974060 title "Contribution of p53-Dependent Caspase Activation to Neuronal Cell Death Declines with Neuronal Maturation" @default.
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• W1680974060 doi "https://doi.org/10.1523/jneurosci.19-08-02996.1999" @default.
• W1680974060 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6782293" @default.
• W1680974060 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10191317" @default.
• W1680974060 hasPublicationYear "1999" @default.
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