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 β‐amyloid peptides (Aβs), remain elusive. We give results to show that lipid peroxidation induced directly by Aβ might be involved in the deficits of nAChRs. In the study, PC12 cells were treated by addition of 5 μM of Aβ~25–35~ and Aβ~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]α‐bungarotoxin binding sites and in the protein levels of the α3 and α7 nAChR subunits were observed in the cells treated with Aβs. Furthermore, Aβ~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 Aβs, the lipid peroxidation and the decreased ubiquinone resulted from Aβs were prohibited. The decreases of nAChR binding sites and subunit proteins resulted from Aβs were mostly prevented by the pretreatment with antioxidant. These findings suggest that lipid peroxidation stimulated by Aβs might be a mechanism for the loss of nAChRs associated with the pathogenesis of AD. © 2002 Wiley‐Liss, Inc.