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