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

Published in Free radical biology & medicine. 2007, vol. 42, no. 7, p. 1062-74
Abstract 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.
Keywords Adenosine Triphosphate/metabolismAnimalsApoptosis/physiologyBlotting, WesternCaspase InhibitorsCaspases/metabolismCell LineCytochromes c/metabolismGlutathione/metabolismHyperoxia/physiopathologyImmunohistochemistryMiceMicroscopy, ElectronMitochondria/physiologyProto-Oncogene Proteins c-bcl-2/physiologyReactive Oxygen Species/metabolism
PMID: 17349933
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Research group Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
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RUCHONNET, Isabelle et al. Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway. In: Free radical biology & medicine, 2007, vol. 42, n° 7, p. 1062-74. doi: 10.1016/j.freeradbiomed.2007.01.008 https://archive-ouverte.unige.ch/unige:43963

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Deposited on : 2014-12-19

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