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  • 标题:Sertindole, a Potent Antagonist at Dopamine D2 Receptors, Induces Autophagy by Increasing Reactive Oxygen Species in SH-SY5Y Neuroblastoma Cells
  • 本地全文:下载
  • 作者:Ji Hyun Shin ; So Jung Park ; Eun Sung Kim
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2012
  • 卷号:35
  • 期号:7
  • 页码:1069-1075
  • DOI:10.1248/bpb.b12-00009
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要: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.
  • 关键词:Sertindole;autophagy;ATG5;reactive oxygen species;SH-SY5Y cell
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