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Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4β2 nAChR-APP695 cells.

Abstract

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.

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  • Publisher Full Text
  • Authors

    , , , , , ,

    Source

    Neurochemical research 36:5 2011 May pg 904-12

    MeSH

    Amyloid Precursor Protein Secretases
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Aspartic Acid Endopeptidases
    Cell Line
    Enzyme-Linked Immunosorbent Assay
    Humans
    Nicotine
    Polymerase Chain Reaction
    Receptors, Nicotinic
    Transcription, Genetic

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21336821

    Citation

    TY - JOUR T1 - Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4β2 nAChR-APP695 cells. AU - Nie,Hui-Zhen, AU - Li,Zuo-Qing, AU - Yan,Qi-Xin, AU - Wang,Ze-Jian, AU - Zhao,Wen-Juan, AU - Guo,Ling-Chen, AU - Yin,Ming, Y1 - 2011/02/19/ PY - 2011/2/3/accepted PY - 2011/2/19/aheadofprint PY - 2011/2/22/entrez PY - 2011/2/22/pubmed PY - 2011/8/17/medline SP - 904 EP - 12 JF - Neurochemical research JO - Neurochem. Res. VL - 36 IS - 5 N2 - 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. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/21336821/Nicotine_decreases_beta_amyloid_through_regulating_BACE1_transcription_in_SH_EP1_α4β2_nAChR_APP695_cells_ L2 - http://dx.doi.org/10.1007/s11064-011-0420-7 ER -