Dopaminergic Toxicity of 1-methyl-4-phenylpyridinium (MPP+): Models for Parkinson's disease (PD) -- restricted access to full text

Fifth Place winner of oral presentations at the 7th Annual Symposium on Graduate Research and Scholarly Projects (GRASP) held at the Marcus Welcome Center, Wichita State University, May 4, 2011.Research completed at the Department of Chemistry, College of Liberal Arts and Sciences1-methyl-4-phenylpyridinium (MPP+) selectively destroys dopaminergic neurons and induces the symptoms similar to Parkinson's disease. The dopaminergic toxicity of MPP+ could be due to dopamine transporter (DAT) uptake and associated inhibition of mitochondrial complex I. The proposed mechanism of MPP+ toxicity is being investigated using MN9D and HepG2 cell models. Our studies show that both cells take-up MPP+ while only MN9D cells are susceptible to MPP+ toxicity. MPP+ toxicity is independent of DAT in MN9D cells. Extracellular calcium and voltage-gated calcium channel blockers decrease the MPP+ uptake into MN9D cells, but do not protect MN9D cells from MPP+ toxicity. These results suggest that the perturbation of intracellular calcium levels by MPP+ may be the cause of toxicity