Scientific article

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

Published inFree radical biology & medicine, vol. 42, no. 7, p. 1062-1074
Publication date2007

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.

  • Adenosine Triphosphate/metabolism
  • Animals
  • Apoptosis/physiology
  • Blotting, Western
  • Caspase Inhibitors
  • Caspases/metabolism
  • Cell Line
  • Cytochromes c/metabolism
  • Glutathione/metabolism
  • Hyperoxia/physiopathology
  • Immunohistochemistry
  • Mice
  • Microscopy, Electron
  • Mitochondria/physiology
  • Proto-Oncogene Proteins c-bcl-2/physiology
  • Reactive Oxygen Species/metabolism
Citation (ISO format)
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. 1062–1074. doi: 10.1016/j.freeradbiomed.2007.01.008
Main files (1)
Article (Published version)
ISSN of the journal0891-5849

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