Inhibiting gene expression of alpha3 nicotinic receptor in SH-SY5Y cells with the effects on APP metabolism and antioxidation in Alzheimer's disease.
Neurochem Int
; 53(5): 112-7, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-18647633
ABSTRACT
In order to examine the effects of alpha3 nicotinic acetylcholine receptor (nAChR) in connection with the pathogenesis of Alzheimer's disease (AD), neuroblastoma (SH-SY5Y) cells were transfected with small interference RNAs (siRNAs) that target specifically towards alpha3 nAChR. The expressions of alpha3 nAChR mRNA and protein were measured by real-time PCR and Western blotting, respectively. The levels of the alpha-form of secreted amyloid precursor protein (alphaAPPs) and total-APP were determined by Western blotting. SH-SY5Y cells transfected with siRNA were then treated with 1muM beta-amyloid peptide (Abeta)(1-42), following which the levels of lipid peroxidation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the reduction rate of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] were characterized by utilizing spectrophotometric procedures. As compared to controls, SH-SY5Y cells transfected with siRNA expressed the decreases in the levels of alpha3 nAChR mRNA and protein by 98% and 66% lower levels, respectively; exhibited reduced level of the alphaAPPs; and demonstrated enhanced lipid peroxidation, decreased rate of MTT reduction, and declined activities of SOD and GSH-Px. Inhibited gene expression of the alpha3 nAChR enhanced the toxicity exerted by Abeta. These results indicate that alpha3 nAChR may improve cleavage of APP by alpha-secretase, enhance antioxidation and inhibit the toxicity of Abeta, suggesting that the receptor might play an important role in AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Receptores Nicotínicos
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Estresse Oxidativo
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Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article