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Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA.
Kalai, M; Van Loo, G; Vanden Berghe, T; Meeus, A; Burm, W; Saelens, X; Vandenabeele, P.
Afiliação
  • Kalai M; Department of Molecular Biomedical Research, Unit of Molecular Signaling and Cell Death, Flanders Interuniversity Institute for Biotechnology and Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Cell Death Differ ; 9(9): 981-94, 2002 Sep.
Article em En | MEDLINE | ID: mdl-12181749
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.
Assuntos
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Bases de dados: MEDLINE Assunto principal: Infecções por Vírus de RNA / Vírus de RNA / RNA de Cadeia Dupla / Transdução de Sinais / Interferons / Apoptose / Células Jurkat / Proteínas Adaptadoras de Transdução de Sinal / Necrose Limite: Animals / Humans Idioma: En Revista: Cell Death Differ Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Bélgica
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Bases de dados: MEDLINE Assunto principal: Infecções por Vírus de RNA / Vírus de RNA / RNA de Cadeia Dupla / Transdução de Sinais / Interferons / Apoptose / Células Jurkat / Proteínas Adaptadoras de Transdução de Sinal / Necrose Limite: Animals / Humans Idioma: En Revista: Cell Death Differ Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Bélgica