Okadaic acid protects human neuroblastoma SH-SY5Y cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis

Neurosci Lett. 2009 Jan 9;449(2):93-7. doi: 10.1016/j.neulet.2008.10.103. Epub 2008 Nov 5.

Abstract

1-methyl-4-phenylpyridinium ion (MPP(+)) has been shown to selectively inhibit mitochondrial function and induce a parkinsonism-like syndrome. MPP(+) stimulates the production of reactive oxygen species (ROS) and induces cell death in vitro. In this study, we investigated the protective effects of okadaic acid on MPP(+)-induced cell death in SH-SY5Y neuroblastoma cells. We found that MPP(+)-induced apoptosis and -ROS generation were blocked by okadaic acid. MPP(+)-mediated activation of AKT was also inhibited by okadaic acid. Taken together, these results demonstrate that okadaic acid protects against MPP(+)-induced apoptosis by blocking ROS stimulation and ROS-mediated signaling pathways in SH-SY5Y cells. These data indicated that okadaic acid could provide a therapeutic strategy for the treatment of neurodegenerative diseases including Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Enzyme Inhibitors / pharmacology
  • Herbicides / antagonists & inhibitors
  • Humans
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neuroblastoma
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Okadaic Acid / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Enzyme Inhibitors
  • Herbicides
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Okadaic Acid
  • Proto-Oncogene Proteins c-akt
  • Protein Phosphatase 2
  • 1-Methyl-4-phenylpyridinium