| Literature DB >> 19944742 |
Maneesh H Singh1, Sheila M Brooke, Ilona Zemlyak, Robert M Sapolsky.
Abstract
Neuronal apoptosis following ischemia can be mediated by a caspase-dependent pathway, which involves the mitochondrial release of cytochrome c that initiates a cascade of caspase activation. In addition, there is a caspase-independent pathway, which is mediated by the release of apoptosis-inducing factor (AIF). Using caspase inhibitor gene therapy, we investigated the roles of caspases on the mitochondrial release of cyt c and the release of AIF. Specifically, we used herpes simplex virus-1 amplicon vectors to ectopically express a viral caspase inhibitor (crmA or p35) in mixed cortical cultures exposed to oxygen/glucose deprivation. Overexpression of either crmA or p35 (but not the caspase-3 inhibitor DEVD) inhibited the release of AIF; this suggests that there can be cross-talk between the caspase-dependent and the ostensibly caspase-independent pathway. In addition, both crmA overexpression and DEVD inhibited cyt c release, suggesting a positive feedback loop involving activated caspases stimulating cyt c release. (c) 2009 Elsevier Ireland Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 19944742 PMCID： PMC2826205 DOI： 10.1016/j.neulet.2009.11.067
Source DB: PubMed Journal: Neurosci Lett ISSN： 0304-3940 Impact factor: 3.046