Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway

被引:112
作者
Metrailler-Ruchonnet, Isabelle
Pagano, Alessandra
Carnesecchi, Stephanie
Ody, Christiane
Donati, Yves
Argiroffo, Constance Barazzone [1 ]
机构
[1] Univ Geneva, Sch Med, Dept Pediat, CH-1211 Geneva, Switzerland
[2] Univ Geneva, Sch Med, Dept Pathol Immunol, CH-1211 Geneva, Switzerland
关键词
hyperoxia; Bcl-2; apoptosis; ROS; caspase;
D O I
10.1016/j.freeradbiomed.2007.01.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bcl-2 is an antiapoptotic molecule that prevents oxidative stress damage and cell death. We investigated the possible protective mechanisms mediated by Bcl-2 during hyperoxia-induced cell death in L929 cells. In these cells, hyperoxia promoted apoptosis without DNA fragmentation. Overexpression of Bcl-2 significantly protected cells from oxygen-induced apoptosis, as shown by measurement of lactate dehydrogenase release, quantification of apoptotic nuclei, and detection of Annexin-V-positive cells. Bcl-2 partially prevented mitochondrial damage and interfered with the mitochondrial proapoptotic signaling pathway: it reduced Bax translocation to mitochondria, decreased the release of cytochrome c, and inhibited caspase 3 activation. However, treatment with the caspase inhibitor Z-VAD.fmk failed to rescue the cells from death) indicating that protection provided by Bcl-2 was due not only to caspase inhibition. Bcl-2 also prevented the release of mitochondrial apoptotic inducing factor, a mediator of caspase-independent apoptosis, correlating with the absence of oligonucleosomal DNA fragmentation. In addition, Bcl-2-overexpressing cells showed significantly higher intracellular amounts of glutathione after 72 h of oxygen exposure. In conclusion, our results demonstrate that the overexpression of Bcl-2 is able to prevent hyperoxia-induced cell death, by affecting mitochondria-dependent apoptotic pathways and increasing intracellular antioxidant compounds. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1062 / 1074
页数:13
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