NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures
1 Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA
2 Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
3 Department of Neurobiology, University of Alabama, Birmingham, AL, USA
4 Center for Neural Science, New York University, New York, NY, USA
Molecular Brain 2009, 2:31 doi:10.1186/1756-6606-2-31Published: 5 October 2009
Previous studies have shown that beta amyloid (Aβ) 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 Aβ (1-42) or nicotine.
We observed that Aβ 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 Aβ and nicotine were blocked by inhibitors of NADPH oxidase.
Our findings indicate that NADPH oxidase-dependent redox signaling is required for Aβ-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease.