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.


CONCLUSIONS
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.
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA. fserrano@bcm.edu
Faridis
F
Serrano
Angela
A
Chang
Caterina
C
Hernandez
Robia G
RG
Pautler
J David
JD
Sweatt
Eric
E
Klann
D000098:Acetophenones / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000098:Acetophenones; D016229:Amyloid beta-Peptides; C579165:Chrna7 protein, rat; D009861:Onium Compounds; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; C007517:diphenyleneiodonium; D009538:Nicotine; C056165:acetovanillone; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D000157:Aconitine