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Title
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Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA
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Author
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Abstract
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| Interferons enhance the cellular antiviral response by inducing expression of protective proteins. Many of these proteins are activated by dsRNA, a typical by-product of viral infection. Here we show that type-I and type-II interferons can sensitize cells to dsRNA-induced cytotoxicity. In caspase-8-or FADD-deficient Jurkat cells dsRNA induces necrosis, instead of apoptosis. In L929sA cells dsRNA-induced necrosis involves high reactive oxygen species production. The antioxidant butylated hydroxyanisole protects cells from necrosis, but shifts the response to apoptosis. Treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-DLAsp(OMe)fluoromethylketone or overexpression of Bcl-2 prevent this shift and promote necrosis. Our results suggest that a single stimulus can initiate different death-signaling pathways, leading to either necrotic or apoptotic cell death. Inhibition of key events in these signaling pathways, such as caspase activation, cytochrome c release or mitochondrial reactive oxygen species production, tips the balance between necrosis and apoptosis, leading to dominance of one of these death programs. |
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Language
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English
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Source (journal)
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Cell death and differentiation. - Oxford
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Publication
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Oxford
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2002
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ISSN
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1350-9047
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DOI
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10.1038/SJ.CDD.4401051
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Volume/pages
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9
:9
(2002)
, p. 981-994
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ISI
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000177583300014
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Full text (Publisher's DOI)
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