Mechanism of 1-methyl-4-phenylpyridinium-induced dopamine release from PC12 cells.

Abstract

The molecular mechanism of 1-methyl-4-phenylpyridinium (MPP+), a Parkinsonism-inducing neurotoxin, has been studied in PC12 cells. The cells treated with MPP+ (100 microM) induced a rapid increase in phosphorylation of tyrosine residues of several proteins, including synaptophysin, a major 38 kDa synaptic vesicle protein implicated in exocytosis. An accelerated release of dopamine by MPP+ correlated with phosphorylation of synaptophysin. Exposing the cells to MPP+ triggered reactive oxygen species (ROS) generation within 60 min of treatment and the said effect was blocked by mazindol, a dopamine uptake blocker. In addition, pretreatment with 50-100 microM of selegiline, a selective MAO-B inhibitor, significantly suppressed MPP+-mediated ROS generation. These effects of MPP+ result in the generation of ROS, which may be involved in neuronal degeneration seen in Parkinson's disease.

• Authors: Jaturaporn Chagkutip, Piyarat Govitrapong, Sirirat Klongpanichpak, Manuchair Ebadi
• Journal: Neurochemical research (Neurochem Res) Vol. 30 Issue 5 Pg. 633-9 (May 2005) ISSN: 0364-3190 [Print] United States
• PMID: 16176067 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dopamine Uptake Inhibitors
• Monoamine Oxidase Inhibitors
• Reactive Oxygen Species
• Synaptophysin
• Selegiline
• Tyrosine
• Mazindol
• 1-Methyl-4-phenylpyridinium
• Calcium
• Dopamine

Topics

• 1-Methyl-4-phenylpyridinium (pharmacology)
• Adrenal Medulla (drug effects, metabolism)
• Animals
• Calcium (metabolism)
• Dopamine (metabolism)
• Dopamine Uptake Inhibitors (pharmacology)
• Exocytosis
• Mazindol (pharmacology)
• Monoamine Oxidase Inhibitors (pharmacology)
• PC12 Cells
• Phosphorylation
• Rats
• Reactive Oxygen Species
• Selegiline (pharmacology)
• Synaptophysin (metabolism)
• Tyrosine (metabolism)