Oxidative stress induced by beta-amyloid peptide(1-42) is involved in the altered composition of cellular membrane lipids and the decreased expression of nicotinic receptors in human SH-SY5Y neuroblastoma cells |
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Authors: | Qi Xiao-Lan Xiu Jin Shan Ke-Ren Xiao Yan Gu Ran Liu Ru-Yu Guan Zhi-Zhong |
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Institution: | aDepartment of Pathology and Molecular Biology, Guiyang Medical College, Guiyang 550004, Guizhou, PR China bNeurotec Department, Division of Molecular Neuropharmacology, Karolinska Institute, SE-14186, Stockholm, Sweden |
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Abstract: | The neurotoxic effects and influence of beta-amyloid peptide (Aβ)1–42 on membrane lipids and nicotinic acetylcholine receptors (nAChRs) in human SH-SY5Y neuroblastoma cells were investigated in parallel. Exposure of the cultured cells to varying concentrations of Aβ1–42 evoked a significantly decrease in cellular reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide), together with enhanced lipid peroxidation and protein oxidation. Significant reductions in the total contents of phospholipid and unbiquinone-10, as well as in the levels of the 3 and 7 subunit proteins of nAChRs were detected in cells exposed to Aβ1–42. In contrast, such treatment had no effect on the total cellular content of cholesterol. Among these alterations, increased lipid peroxidation and decreased levels of cellular phospholipids were most sensitive to Aβ1–42, occurring at lower concentrations. In addition, when SH-SY5Y cells were pretreated with the antioxidant Vitamin E, prior to the addition of Aβ1–42, these alterations in neurotoxicity, oxidative stress, composition of membrane lipids and expression of nAChRs were partially prevented. These findings suggest that stimulation of lipid peroxidation by Aβ may be involved in eliciting the alterations in membrane lipid composition and the reduced expression of nAChRs associated with the pathogenesis of AD. |
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Keywords: | Alzheimer's disease Beta-amyloid peptides Lipid peroxidation Membrane lipids Nicotinic acetylcholine receptor SH-SY5Y cells |
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