Amurensin G induces autophagy and attenuates cellular toxicities in a rotenone model of Parkinson's disease.

ABSTRACT

Although Parkinson's disease is a common neurodegenerative disorder its cause is still unknown. Recently, several reports showed that inducers of autophagy attenuate cellular toxicities in Parkinson's disease models. In this report we screened HEK293 cells that stably express GFP-LC3, a marker of autophagy, for autophagy inducers and identified amurensin G, a compound isolated from the wild grape (Vitis amurensis). Amurensin G treatment induced punctate cytoplasmic expression of GFP-LC3 and increased the expression level of endogenous LC3-II. Incubation of human dopaminergic SH-SY5Y cells with amurensin G attenuated the cellular toxicities of rotenone in a model of Parkinson's disease. Amurensin G inhibited rotenone-induced apoptosis and interfered with rotenone-induced G2/M cell cycle arrest. In addition, knockdown of beclin1, a regulator of autophagy, abolished the effect of amurensin G. These data collectively indicate that amurensin G attenuates cellular toxicities through the induction of autophagy.