Nicotine Decreases Beta-Amyloid Through Regulating BACE1 Transcription in SH-EP1-α4β2 nAChR-APP695 Cells
| Autor: | Wenjuan Zhao, Qi-Xin Yan, Zuo-Qing Li, Huizhen Nie, Zejian Wang, Lingchen Guo, Ming Yin |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Nicotine
Transcription Genetic Protein subunit Enzyme-Linked Immunosorbent Assay Receptors Nicotinic Pharmacology Biology Polymerase Chain Reaction Biochemistry Cell Line Amyloid beta-Protein Precursor Cellular and Molecular Neuroscience mental disorders medicine Aspartic Acid Endopeptidases Humans Receptor Reporter gene Amyloid beta-Peptides General Medicine Transfection Cell biology Nicotinic agonist Cell culture Epibatidine Amyloid Precursor Protein Secretases medicine.drug |
| Zdroj: | Neurochemical Research. 36:904-912 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/s11064-011-0420-7 |
| Popis: | Alzheimer's disease (AD) is a neurodegenerative disorder that affects the elderly population. Deposition of beta-amyloid (Aβ) in the brain is a hallmark of AD pathology. In our previous study, we have constructed a cell line expressing human APP695 (hAPP695) in SH-EP1 cells stably transfected with human nicotinic receptor (nAChR) α4 subunit and β2 subunit gene. In present study, we found that activation of α4β2 nAChR by nicotine and epibatidine decreased secreted Aβ level in the cell line and hippocampal neurons, but had no effects on full-length APP695 and sAPP-α. Nicotine also decreases BACE1 and PSEN1 expression, as well as ERK1 and NFκB P65 subunit expression in the cell line. Furthermore, BACE1 promoter activity is, but PSEN1 not, decreased by nicotine in the cell line. All the results suggest that activation of α4β2 nAChR decreases Aβ through regulating BACE1 transcription by ERK1-NFκB pathway. Additionally, analysis of BACE1 promoter activity by dual-luciferase reporter assay may be useful for drug screening as a high throughput method. |
| Databáze: | OpenAIRE |
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