Fraxetin prevents rotenone-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells

Neurosci Res. 2005 Sep;53(1):48-56. doi: 10.1016/j.neures.2005.05.009.

Abstract

Fraxetin belongs to an extensive group of natural phenolic anti-oxidants. In the present study, using a human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on rotenone-mediated cytoxicity. Incubation of cells with the fraxetin led to a significant elevation dose-dependent of cellular GSH and this was accompanied by a marked protection against rotenone-mediated toxicity, which was also significantly reversed in the cells with buthionine sulfoximine (BSO) co-treatment. Taken together, this study suggested that intracellular GSH appeared to be an important factor in fraxetin-mediated cytoprotection against rotenone-toxicity in SH-SY5Y cells. Fraxetin at 10-100 muM inhibited the formation of ROS, cytochrome c release, activation of caspase-3 and 9, and suppressed the up-regulation of Bax, whereas no significant change occurred in Bcl-2 levels. Our results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against rotenone-induced cytotoxicity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspases / metabolism
  • Cell Count
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coumarins / pharmacology*
  • Cytochromes c / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism*
  • Humans
  • Insecticides / toxicity*
  • Mitochondria / drug effects
  • Neuroblastoma
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Rotenone / toxicity*

Substances

  • Coumarins
  • Insecticides
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Rotenone
  • Cytochromes c
  • fraxetin
  • Caspases
  • Glutathione