Feedback regulation of SREBP and aromatase in A beta(25-35)-supplemented human neuroblastoma cells.

1. The analogies between the processing of amyloid precursor protein (APP) and other transmembrane sterol regulatory element binding proteins (SREBPs) inspired us to conduct further studies on whether beta-amyloid (Abeta) affects aromatase by interacting with APP and SREBP. 2. In this study, cultured human neuroblastoma cells (SHSY-5Y) were incubated in experimental media (media without FBS, the main cholesterol source) in the presence or absence of Abeta (1 microM) for 24 h. 3. Cellular extracts were subjected to immunoblot analysis using anti-APP, anti-aromatase and anti-SREBP-1. In these cell lines, we detected aromatase (55 kDa), SREBP cleavage product (68 kDa) and APP precursor (100-95 kDa) and cleavage product (60 kDa) by immunoblotting. Aromatase and SREBP levels were elevated in the cells incubated 24 h in experimental media and were attenuated in Abeta-supplemented experimental media. 4. The disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimer's disease. These findings may have important implications for understanding the mechanisms of the aromatase enzyme gene in disease states such as Alzheimer's.