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Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells

M R Ciriolo1, A De Martino, E Lafavia

  • 1Department of Biomedical Sciences, University of Chieti "G. D'Annunzio," via dei Vestini, 66100 Chieti, Italy. Ciriolo@bio.uniroma2.it

The Journal of Biological Chemistry
|February 15, 2000
PubMed

Insights

Nitric oxide causes neuroblastoma cell death (apoptosis). The integrity of copper, zinc-superoxide dismutase (Cu,Zn-SOD) is crucial for resistance, as its mutation increases cell death by altering reactive oxygen and nitrogen species balance.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Nitric oxide (NO) induces apoptosis in human neuroblastoma cells (SH-SY5Y).
  • Early signs include p53 and p21 accumulation, indicating S-nitrosoglutathione toxicity.
  • Mitochondrial cytochrome c release and caspase 3 activation are key apoptotic events.

Purpose of the Study:

  • To investigate the role of copper, zinc-superoxide dismutase (Cu,Zn-SOD) integrity in NO-mediated apoptosis of neuroblastoma cells.
  • To determine how Cu,Zn-SOD influences reactive oxygen species (ROS) and reactive nitrogen species (RNS) balance in this context.

Main Methods:

  • Transfection of SH-SY5Y cells with wild-type (WT) or mutant (G93A) Cu,Zn-SOD.
  • Measurement of nitrite/nitrate production, apoptosis levels, Bcl-2 expression, and ROS levels.
  • Assessment of cytochrome c oxidase activity.

Main Results:

  • G93A mutant Cu,Zn-SOD cells exhibited increased apoptosis compared to WT cells, despite similar NO production.
  • WT cells showed higher Bcl-2 levels and decreased ROS, correlating with protection from apoptosis.
  • G93A cells displayed reduced Bcl-2, elevated ROS, and lower cytochrome c oxidase activity, indicating susceptibility.

Conclusions:

  • Neuroblastoma cell apoptosis resistance is directly linked to the level and integrity of Cu,Zn-SOD.
  • The balance between ROS and RNS, modulated by Cu,Zn-SOD, is a critical regulator of NO-induced neuroblastoma apoptosis.

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