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DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation.
Huang, Huey-Lan; Fang, Li-Wen; Lu, Shu-Ping; Chou, Chen-Kung; Luh, Tien-Yau; Lai, Ming-Zong.
Afiliação
  • Huang HL; Institute of Molecular Biology, Academia Sinica, Taiwan.
Oncogene ; 22(50): 8168-77, 2003 Nov 06.
Article em En | MEDLINE | ID: mdl-14603257
DNA-damaging reagents may kill tumor cells through the generation of reactive oxygen species (ROS). Cytotoxic reagents may also induce apoptosis of cancer cells in Fas-FADD-dependent manners. In this study, we explored the possible link between these two apparently distinct pathways in T leukemia cell Jurkat. Our results demonstrated that gamma-irradiation, similar to cisplatin, induced apoptosis by triggering Fas aggregation and activating FADD-caspase-8 apoptotic cascade. The absence of caspase-8 or Fas greatly reduced the sensitivity to apoptosis mediated by DNA-damaging agents. In addition, apoptosis induced by cisplatin and gamma-irradiation, but not by Fas, was inhibited by ROS scavengers, including N-acetyl cysteine, MnTBAP, and C60. Importantly, these ROS scavengers effectively prevented the clustering of Fas receptor induced by cisplatin and gamma-irradiation. Our results suggest that cisplatin and gamma-irradiation promote ROS production, which in turn contributes to Fas receptor aggregation and cell death. The novel coupling between ROS and Fas clustering likely plays a significant role in apoptosis triggered by DNA-damaging reagents in Fas-expressing leukemia cells.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Espécies Reativas de Oxigênio / Apoptose / Receptor fas / Proteínas Adaptadoras de Transdução de Sinal Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Espécies Reativas de Oxigênio / Apoptose / Receptor fas / Proteínas Adaptadoras de Transdução de Sinal Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article