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  • 标题:DHA Hydroperoxides as a Potential Inducer of Neuronal Cell Death: a Mitochondrial Dysfunction-Mediated Pathway
  • 本地全文:下载
  • 作者:Xuebo Liu ; Takahiro Shibata ; Shinsuke Hisaka
  • 期刊名称:Journal of Clinical Biochemistry and Nutrition
  • 印刷版ISSN:0912-0009
  • 电子版ISSN:1880-5086
  • 出版年度:2008
  • 卷号:43
  • 期号:1
  • 页码:26-33
  • DOI:10.3164/jcbn.2008040
  • 出版社:The Society for Free Radical Research Japan
  • 摘要:During the lipid peroxidation reaction, lipid hydroperoxides are formed as primary products. Several lines of evidence suggest that lipid hydroperoxides can trigger cell death in many cell types, including neurons. In a screening of lipid hydroperoxides which can induce toxicity in neuronal cells, we found docosahexaenoic acid hydroperoxides (DHA-OOH) induced much severe levels of reactive oxygen species generation and cell death in human neuroblastoma SH-SY5Y cells compared to the hydroperoxides of linoleic acid and arachidonic acid. Therefore, we focused on DHA-OOH, and demonstrated that DHA-OOH apparently induced an apoptosis in the neuronal cells through several apoptotic hallmarks including nuclei condensation, DNA fragmentation, poly (ADP-ribose) polymerase cleavage and increased activity of caspase-3. We also found the signaling changes in mitochondria-mediated apoptosis, such as cytochrome c release and increased expression of Bcl-2, as well as a dose-dependent attenuation of mitochondrial membrane potential in the DHA-OOH treated cells. These data indicated DHA hydroperoxide as a potential inducer of apoptosis in human neuroblastoma SH-SY5Y cells, which may be mediated by mitochondria dysfunction pathway.
  • 关键词:lipid peroxidation;DHA hydroperoxides;apoptosis;mitochondria dysfunction;neurodegeneration
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