Gliotoxin induces apoptosis in cultured macrophages via production of reactive oxygen species and cytochrome c release without mitochondrial depolarization.
Free Radic Res
; 35(1): 1-10, 2001 Jul.
Article
em En
| MEDLINE
| ID: mdl-11697112
ABSTRACT
The cytotoxicity and its underlying mechanisms induced by gliotoxin (GT), an immunosuppressive agent, in macrophages are poorly understood. We report here that GT induced a rapid apoptosis (DNA fragmentation and hypodiploid nuclei obtained within 4 hrs of treatment) in murine macrophages PU5-1.8 in a dose-dependent and cell cycle-independent manner. The GT-induced apoptosis was suppressed by z-Asp, z-VAD-fmk and antioxidants suggesting that production of reactive oxygen species (ROS) and activation of caspases were important in this process. Also, release of cytochrome c from mitochondria was found to be an early event (within 1 hr) after addition of GT (250 ng/ml) and its presence in the cytosol was sufficient to elicit apoptosis. Interestingly, the release of cytochrome c was not accompanied by a reduction in the mitochondrial membrane potential (psi m) as determined by several psi m-sensitive fluorescent indicators. Taken together, our results indicate that GT is a potent apoptotic agent in PU5-1.8 cells and the loss of psi m is not a universal early marker for apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
/
Apoptose
/
Grupo dos Citocromos c
/
Etídio
/
Gliotoxina
/
Imunossupressores
/
Macrófagos
/
Mitocôndrias
Limite:
Animals
Idioma:
En
Revista:
Free Radic Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
China