Fischer Barbara, Coelho David, Dufour Patrick, Bergerat Jean Pierre, Denis Jean Marc, Gueulette John, Bischoff Pierre
Laboratoire de Cancérologie Expérimentale et de Radiobiologie EA 3430, Université Louis Pasteur, Institut de Recherche contre les Cancers de l'Appareil Digestif, Strasbourg, France.
Biochem Biophys Res Commun. 2003 Jun 27;306(2):516-22. doi: 10.1016/s0006-291x(03)01004-0.
The objective of this study was to characterize the apoptotic pathways activated by fast neutrons in the human lymphoblastoid cell line TK6 and in its p53 -/- derivative. Our results demonstrate that while p53 is not required for neutron-induced apoptosis, as previously shown, it does affect the kinetics of apoptosis and the molecular pathways leading to the activation of effector caspases. Indeed, rapid p53-dependent apoptosis was associated with the activation of caspase 9, 8, 3, and 7 and the cleavage of BID by caspase 8. In contrast, the slow-occurring p53-independent apoptotic process, mediated by caspase 7, took place without BID cleavage and loss of transmembrane mitochondrial potential. Altogether, our findings highlight an essential role for caspase 8-mediated BID cleavage, in the course of p53-dependent apoptosis triggered by fast neutrons in lymphoid cells. They also demonstrate that this mechanism is not involved in p53-independent apoptosis.
本研究的目的是阐明快中子在人淋巴母细胞系TK6及其p53基因敲除衍生物中激活的凋亡途径。我们的结果表明，如先前所示，虽然p53不是中子诱导凋亡所必需的，但它确实会影响凋亡动力学以及导致效应半胱天冬酶激活的分子途径。事实上，快速的p53依赖性凋亡与半胱天冬酶9、8、3和7的激活以及半胱天冬酶8对BID的切割有关。相反，由半胱天冬酶7介导的缓慢发生的p53非依赖性凋亡过程，在没有BID切割和跨膜线粒体电位丧失的情况下发生。总之，我们的研究结果突出了半胱天冬酶8介导的BID切割在淋巴样细胞中由快中子触发的p53依赖性凋亡过程中的重要作用。它们还表明，这种机制不参与p53非依赖性凋亡。
