title: Influence of cholesterol and lovastatin on alpha-form of secreted amyloid precursor protein and expression of alpha7 nicotinic receptor on astrocytes.
abstract: The influence of cholesterol and the lovastatin (cholesterol-lowering drug) on secretion of alpha-secretase cleavage product of amyloid precursor protein (APP) and expression of nicotinic acetylcholine receptors (nAChRs) was investigated in human HTB-15 astrocytes. The results showed that exposure of cholesterol to astrocytes inhibited the secretion of alpha-form of secreted APP (alphaAPPs) and reduced cell viability, while lovastatin enhanced the alpha-secretase processing on astrocytes; cholesterol treatment decreased expression of alpha7 nAChR, whereas lovastatin induced an up-regulation of the receptor; the increase in alphaAPPs resulted from lovastatin was partially inhibited by the alpha7 nAChR antagonists, alpha-bungarotoxin or methyllycaconitine; cholesterol or lovastatin did not influence either whole APP level or expression of alpha4 nAChR. We suggest that high dose of cholesterol may inhibit both the activity of alpha-secretase in APP metabolic processing and the expression of alpha7 nAChR, while lovastatin may stimulate alpha-secretase cleavage processing that might be regulated by alpha7 nAChR.
authors: Karolinska Institutet, Neurotec Department, Division of Molecular Neuropharmacology, 141 86 Stockholm, Sweden.
authors: Jin
authors: J
authors: Xiu
authors: Agneta
authors: A
authors: Nordberg
authors: Xiaolan
authors: X
authors: Qi
authors: Zhi-Zhong
authors: ZZ
authors: Guan