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2008 | 55 | 2 | 339-347
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Molecular mechanism of PC12 cell death evoked by sodium nitroprusside, a nitric oxide donor

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Nitric oxide (NO) is a potent extracellular and intracellular physiological messenger. However, NO liberated in excessive amounts can be involved in macromolecular and mitochondrial damage in brain aging and in neurodegenerative disorders. The molecular mechanism of its neurotoxic action is not fully understood. Our previous data indicated involvement of NO in the release of arachidonic acid (AA), a substrate for cyclo- and lipoxygenases (COX and LOX, respectively). In this study we investigated biochemical processes leading to cell death evoked by an NO donor, sodium nitroprusside (SNP). We found that SNP decreased viability of pheochromocytoma (PC12) cells in a concentration- and time-dependent manner. SNP at 0.1 mM caused a significant increase of apoptosis-inducing factor (AIF) protein level in mitochondria. Under these conditions 80% of PC12 cells survived. The enhancement of mitochondrial AIF level might protect most of PC12 cells against death. However, NO released from 0.5 mM SNP induced massive cell death but had no effect on protein level and localization of AIF and cytochrome c. Caspase-3 activity and poly(ADP-ribose) polymerase-1 (PARP-1) protein levels were not changed. However, PARP activity significantly decreased in a time-dependent manner. Inhibition of both COX isoforms and of 12/15-LOX significantly lowered the SNP-evoked cell death. We conclude that AIF, cytochrome c and caspase-3 are not responsible for the NO-mediated cell death evoked by SNP. The data demonstrate that NO liberated in excess decreases PARP-1 activity. Our results indicate that COX(s) and LOX(s) are involved in PC12 cell death evoked by NO released from its donor, SNP.
Physical description
  • Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Department of Cellular Signaling, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Department of Neurosurgery, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
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