title: Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells.
abstract: A line of evidence has shown that a link between the common pathological features of beta-amyloid peptide (Abeta) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to Abeta can decrease expression of nicotinic acetylcholine receptors (nAChRs), which have been shown to play roles in brain cognitive functions. Here, we report that treatment with Abeta1-40 and Abeta25-35 at nanomolar concentrations significantly decreased the [3H]epibatidine and [125I]alpha-bungarotoxin binding sites, the protein and mRNA levels of nAChR alpha3, alpha7 and beta2 subunits in PC12 cells. Abeta1-40 and Abeta25-35 at the concentrations used in the treatment study neither bound to nAChRs nor induced apoptosis, but significantly inhibited the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by Abeta may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that Abeta can degenerate nAChRs early in the course of AD before the formation of abundant Abeta fibrils.
authors.affiliation: Division of Molecular Neuropharmacology, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Guan
authors.forename: H
authors.initials: H
authors.lastname: Miao
authors.forename: J Y
authors.initials: JY
authors.lastname: Tian
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: A
authors.initials: A
authors.lastname: Nordberg
authors.forename: X
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000109:Acetylcholine; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579165:Chrna7 protein, rat; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)