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Oligomeric aggregates of amyloid beta peptide 1-42 activate ERK/MAPK in SH-SY5Y cells via the alpha7 nicotinic receptor
- Source :
- Neurochemistry international. 55(8)
- Publication Year :
- 2009
-
Abstract
- The production and aggregation of amyloid beta peptides (Abeta) has been linked to the development and progression of Alzheimer's disease. It is apparent that the various structural forms of Abeta can affect cell signalling pathways and the activity of neurons differently. In this study, we investigated the effects of oligomeric and fibrillar aggregates of Abeta 1-42 (Abeta42) and non-aggregated peptide upon activation of the ERK/MAPK signalling pathway. In SH-SY5Y cells, acute exposure to oligomeric Abeta42 led to phosphorylation of ERK1/2 at concentrations as low as 1 nM and up to 100 nM. These changes were detected as early as 5 min following exposure to 100 nM oligomeric Abeta42, reaching a maximum level after 10 min. Phosphorylation of ERK1/2 subsequently declined to and remained at basal levels after 30 min to 2h of exposure. Fibrillar aggregates of Abeta42 did not significantly induce phosphorylation of ERK1/2 and non-aggregated Abeta42 did not activate the pathway. The effects of oligomeric Abeta42 to increase ERK phosphorylation above basal levels were inhibited by MLA, a specific antagonist of the alpha7 nAChR. U0126, an inhibitor of MEK, the upstream activator of ERK1/2, completely blocked induction of ERK1/2 phosphorylation. Oligomeric aggregates of Abeta42 are the principal structural form of the peptide that activates ERK/MAPK in SH-SY5Y cells and these effects are mediated by the alpha7 nAChR.
- Subjects :
- MAPK/ERK pathway
Cell signaling
Time Factors
alpha7 Nicotinic Acetylcholine Receptor
Amyloid beta
MAP Kinase Signaling System
Polymers
MAP Kinase Kinase 1
Peptide
Nicotinic Antagonists
Receptors, Nicotinic
Cellular and Molecular Neuroscience
Alzheimer Disease
Cell Line, Tumor
mental disorders
Humans
Enzyme Inhibitors
Phosphorylation
chemistry.chemical_classification
Neurons
Amyloid beta-Peptides
Mitogen-Activated Protein Kinase 3
biology
Dose-Response Relationship, Drug
Activator (genetics)
Chemistry
P3 peptide
Neurofibrillary Tangles
Cell Biology
Molecular biology
Peptide Fragments
nervous system diseases
Cell biology
Enzyme Activation
nervous system
Mitogen-activated protein kinase
biology.protein
Subjects
Details
- ISSN :
- 18729754
- Volume :
- 55
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Neurochemistry international
- Accession number :
- edsair.doi.dedup.....d9c3690c76a306c848d51fc497e22574