Apoptosis provoked by the oxidative stress inducer menadione (Vitamin K(3)) is mediated by the Fas/Fas ligand system.
Clin Immunol
; 93(1): 65-74, 1999 Oct.
Article
en En
| MEDLINE
| ID: mdl-10497012
ABSTRACT
Menadione, or vitamin K(3) (VK(3)), a potent oxidative stress inducer, has been recently used as an effective and remarkably safe cytotoxic drug for treatment of several human tumors. VK(3) induces apoptotic cell death through a poorly understood mechanism. Here we show for the first time that VK(3)-induced apoptosis requires the Fas/FasL system. Spleen cells from both Fas- and FasL-deficient mice (C57BL/6-lpr and C57BL/6-gld, respectively) had much lower levels of VK(3) apoptosis in vitro compared to cells from control C57BL/6 mice. VK(3) cytotoxicity toward mouse splenocytes was also blocked with a Fas-Fc fusion protein. VK(3) induced apoptosis in Jurkat cells, coincident with an increase in both Fas and FasL expression. A FasL-resistant variant of these Jurkat cells was also resistant to VK(3)-induced apoptosis. Furthermore, because VK(3) effects were inhibited by glutathione, a potent antioxidant, oxidative stress was linked to the Fas/FasL system. Moreover, since the Jurkat cell lines were p53 null, the activation of Fas/FasL system after oxidative stress apparently acted through a p53-independent pathway. The therapeutic relevance of the K vitamins has been growing in recent years; our findings offer new insight for improving and expanding their applications.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vitamina K
/
Glicoproteínas de Membrana
/
Apoptosis
/
Estrés Oxidativo
/
Receptor fas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos