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

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.

• Authors: Kook-Hee Ahn, Young-Sun Kim, Seon-Ye Kim, Youngbuhm Huh, Chan Park, Joo-Won Jeong
• Journal: Neuroscience letters (Neurosci Lett) Vol. 449 Issue 2 Pg. 93-7 (Jan 09 2009) ISSN: 0304-3940 [Print] Ireland
• PMID: 19000740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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