Amyloid-beta(1-42) Induces Reactive Oxygen Species-Mediated Autophagic Cell Death in U87 and SH-SY5Y Cells

Alzheimer's disease (AD) is a neurodegenerative disorder initiated by the aggregation of amyloid-beta peptide (A beta). Macroautophagy, which is essential for cell survival as well as the promotion of cell death, has been observed extensively in AD brains or transgenic mice overexpressing A beta protein precursor. However, the role of macroautophagy in the pathogenesis of AD is unclear. In this study, we showed that A beta(1-42) triggered autophagic cell death in both human glioma cell line (U87 cell) and human neuroblastoma cell line (SH-SY5Y cell). A beta(1-42)-induced cytotoxicity and autophagic cell death were blocked by the autophagy inhibitor 3-methyladenine (3-MA) or by small interfering RNA against the autophagy gene Beclin-1. Reactive oxygen species (ROS) accumulation was also detected in both A beta(1-42) treated cell lines and this accumulation was not affected by 3-MA. Moreover, pretreatment with the ROS scavenger N-acetylcysteine inhibited ROS accumulation and autophagic cell death induced by A beta(1-42), suggesting that A beta(1-42)-induced ROS accumulation might trigger the onset of autophagy and subsequent autophagic cell death. These findings provide further insights into the mechanisms underlying A beta-induced cytotoxicity.