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 μM) 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 μM 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. © 2005 Springer Science+Business Media, Inc.