Okadaic acid protects human neuroblastoma SH-SY5Y cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis.
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.
Ahn
Kook-Hee
KH
Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kim
Young-Sun
YS
Kim
Seon-Ye
SY
Huh
Youngbuhm
Y
Park
Chan
C
Jeong
Joo-Won
JW
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006540:Herbicides / Q000037:antagonists & inhibitors; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006540:Herbicides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019319:Okadaic Acid; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D015655:1-Methyl-4-phenylpyridinium