Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA.
Cell Death Differ
; 9(9): 981-94, 2002 Sep.
Article
in En
| MEDLINE
| ID: mdl-12181749
ABSTRACT
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-DL-Asp(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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Virus Infections
/
RNA Viruses
/
RNA, Double-Stranded
/
Signal Transduction
/
Interferons
/
Apoptosis
/
Jurkat Cells
/
Adaptor Proteins, Signal Transducing
/
Necrosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Death Differ
Year:
2002
Document type:
Article
Affiliation country:
Belgium