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Biol Pharm Bull. 2012;35(7):1069-75.

Sertindole, a potent antagonist at dopamine D₂ receptors, induces autophagy by increasing reactive oxygen species in SH-SY5Y neuroblastoma cells.

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1
Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-do 446-701, Korea.

Abstract

Autophagy is associated with cell survival and cell death. Autophagy is implicated in the pathophysiology of various human diseases. In order to identify autophagy regulatory molecules, we screened a chemical drug library in SH-SY5Y cells and selected Sertindole as a potent autophagy inducer. Sertindole was developed as an antipsychotic drug for Schizophrenia. Sertindole treatment highly induced the formation of autophagosomes as well as LC3 conversion. Subsequently, Sertindole-induced autophagy was efficiently suppressed by down regulation of ATG5. Sertindole also increased reactive oxygen species (ROS) production, which contributes to autophagy-associated cell death in neuroblastoma cells. ROS scavengers such as N-acetylcysteine and Trolox suppressed not only ROS generation but also autophagy activation by Sertindole. These results suggest Sertindole induces autophagy and autophagy-associated cell death by ROS production in neuroblastoma cells.

PMID:
22791154
[Indexed for MEDLINE]
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