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.
The neurotoxic effects and influence of beta-amyloid peptide (Abeta)(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 Abeta(1-42) 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 ubiquinone-10, as well as in the levels of the alpha3 and alpha7 subunit proteins of nAChRs were detected in cells exposed to Abeta(1-42). 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 Abeta(1-42), occurring at lower concentrations. In addition, when SH-SY5Y cells were pretreated with the antioxidant Vitamin E, prior to the addition of Abeta(1-42), 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 Abeta may be involved in eliciting the alterations in membrane lipid composition and the reduced expression of nAChRs associated with the pathogenesis of AD.
Qi
Xiao-Lan
XL
Department of Pathology and Molecular Biology, Guiyang Medical College, Guiyang 550004, Guizhou, PR China.
Xiu
Jin
J
Shan
Ke-Ren
KR
Xiao
Yan
Y
Gu
Ran
R
Liu
Ru-Yu
RY
Guan
Zhi-Zhong
ZZ
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D002784:Cholesterol; D008563:Membrane Lipids; D010446:Peptide Fragments; D010743:Phospholipids; D011978:Receptors, Nicotinic; D014451:Ubiquinone; D014810:Vitamin E; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C075222:amyloid beta-protein (1-42)