Background: Nitric oxide (NO•) is known to be both neurotoxic and neuroprotective. There are three redox-related species: neutral NO•, the nitroxyl anion (NO-) and the nitrosonium cation(NO+).

Subjects and Interventions: Differentiated PC12 cells were treated with increasing concentrations (0.001 to 5 mM) of NO•, NO+, and NO-, in the presence or absence of nerve growth factor(NGF).

Results: Low concentrations (up to 100 μM) of NO• and NO+ inhibited apoptosis after NGF withdrwal, while NO- did not. In the presence of NGF, higher concentrations (above 300 μM) of NO• and NO+ induced apoptosis while NO- treatment resulted in necrosis.

Conclusion: Nitric oxide can be neuroprotective or neurotoxic, depending on the redox state of the molecule. NO• and NO+ induce apoptosis, while NO- induces necrosis in PC12 cells.