title: Loss of nicotinic receptors induced by beta-amyloid peptides in PC12 cells: possible mechanism involving lipid peroxidation.
abstract: The mechanisms involved in the loss of nicotinic acetylcholine receptors (nAChRs), seen in brains of patients with Alzheimer's disease (AD) and in cultured cells treated by beta-amyloid peptides (A betas), remain elusive. We give results to show that lipid peroxidation induced directly by A beta might be involved in the deficits of nAChRs. In the study, PC12 cells were treated by addition of 5 microM of A beta(25-35) and A beta(1-40), respectively, with or without a antioxidant, vitamin E. Besides significantly decreased MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide) reduction, an increased lipid peroxidation was detected in the cells, but no protein oxidation. Significant reductions in [(3)H]epibatidine and [(125)I]alpha-bungarotoxin binding sites and in the protein levels of the alpha 3 and alpha 7 nAChR subunits were observed in the cells treated with A betas. Furthermore, A beta(25-35) decreased the level of ubiquinone-9 in PC12 cells, but did not change the amount of cholesterol, providing further evidence for lipid peroxidation. Interestingly, when PC12 cells were pretreated by antioxidant before the addition of A betas, the lipid peroxidation and the decreased ubiquinone resulted from A betas were prohibited. The decreases of nAChR binding sites and subunit proteins resulted from A betas were mostly prevented by the pretreatment with antioxidant. These findings suggest that lipid peroxidation stimulated by A betas might be a mechanism for the loss of nAChRs associated with the pathogenesis of AD.
authors.affiliation: Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Molecular Neuropharmacology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. zhizhong.guan@neurotec.ki.se
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Yu
authors.forename: Ke-Ren
authors.initials: KR
authors.lastname: Shan
authors.forename: Tomas
authors.initials: T
authors.lastname: Nordman
authors.forename: Jerker
authors.initials: J
authors.lastname: Olsson
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25)