Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor.
J Exp Med
; 187(9): 1477-85, 1998 May 04.
Article
en En
| MEDLINE
| ID: mdl-9565639
ABSTRACT
Murine L929 fibrosarcoma cells treated with tumor necrosis factor (TNF) rapidly die in a necrotic way, due to excessive formation of reactive oxygen intermediates. We investigated the role of caspases in the necrotic cell death pathway. When the cytokine response modifier A (CrmA), a serpin-like caspase inhibitor of viral origin, was stably overexpressed in L929 cells, the latter became 1,000-fold more sensitive to TNF-mediated cell death. In addition, TNF sensitization was also observed when the cells were pretreated with Ac-YVAD-cmk or zDEVD-fmk, which inhibits caspase-1- and caspase-3-like proteases, respectively. zVAD-fmk and zD-fmk, two broad-spectrum inhibitors of caspases, also rendered the cells more sensitive, since the half-maximal dose for TNF-mediated necrosis decreased by a factor of 1,000. The presence of zVAD-fmk also resulted in a more rapid increase of TNF-mediated production of oxygen radicals. zVAD-fmk-dependent sensitization of TNF cytotoxicity could be completely inhibited by the oxygen radical scavenger butylated hydroxyanisole. These results indicate an involvement of caspases in protection against TNF-induced formation of oxygen radicals and necrosis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inhibidores de Cisteína Proteinasa
/
Factor de Necrosis Tumoral alfa
/
Caspasas
/
Necrosis
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
1998
Tipo del documento:
Article
País de afiliación:
Bélgica