NADPH oxidase mediates beta-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures.

BACKGROUND

Previous studies have shown that beta amyloid (Abeta) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either Abeta (1-42) or nicotine.

RESULTS

We observed that Abeta and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by Abeta and nicotine were blocked by inhibitors of NADPH oxidase.

CONCLUSION

Our findings indicate that NADPH oxidase-dependent redox signaling is required for Abeta-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease.