Aim: To observe the relationship between amyloid beta-protein (Abeta) and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide (PACAP, PACAP-27) against damage induced by oxidative stress (H2O2) in neurem-2a cells.

Methods: With cultured neuro-2a cells the cell survival and apoptosis were measured by MTT assay, Hoechest33258 staining, DNA ladder and the percentage of small DNA fragment.

Results: Concentration-dependent toxicity was induced with H2O2 treatment for 24 h. The neurotoxicity of H2O2 was increased by about 10 times with cotreatment neurons with amyloid beta-protein fragment 25-35 (Abeta(25-35)). While decrease the percentage of small DNA fragmentation the cell survival was increased with co-treatment with PACAP-27(which were added to the culture everyday). The effect of PACAP was not reversed with antagonist of PACAP receptor, PACAP(6-27).

Conclusion: Abeta and H2O2 can promote each other's neurotoxicity. Cultured neurons were protected by PACAP27 from the neurotoxicity of H2O2 but not through the activation of PACAP-27 receptor.

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