Influence of cholesterol and lovastatin on α-form of secreted amyloid precursor protein and expression of α7 nicotinic receptor on astrocytes

The influence of cholesterol and the lovastatin (cholesterol-lowering drug) on secretion of α-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 α-form of secreted APP (αAPPs) and reduced cell viability, while lovastatin enhanced the α-secretase processing on astrocytes; cholesterol treatment decreased expression of α7 nAChR, whereas lovastatin induced an up-regulation of the receptor; the increase in αAPPs resulted from lovastatin was partially inhibited by the α7 nAChR antagonists, α-bungarotoxin or methyllycaconitine; cholesterol or lovastatin did not influence either whole APP level or expression of α4 nAChR. We suggest that high dose of cholesterol may inhibit both the activity of α-secretase in APP metabolic processing and the expression of α7 nAChR, while lovastatin may stimulate α-secretase cleavage processing that might be regulated by α7 nAChR.