Nimodipine attenuates the parkinsonian neurotoxin, MPTP-induced changes in the calcium binding proteins, calpain and calbindin

Abstract

We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP+)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). mRNA and protein levels of calbindin were lower, while that of calpain were higher in MPP+-treated SH-SY5Y cells and MPTP-treated mouse striatum as compared to their respective controls. Nimodipine pretreatment significantly attenuated these effects in the parkinsonian neurotoxin-treated SH-SY5Y cell line and in the mouse striatum. The activities of the apoptotic mediator, caspase-3 and calpain were increased in the neurotoxin-treated groups as compared to their respective controls, which was ameliorated by nimodipine pretreatment. These results suggest that parkinsonian neurotoxin-mediated dopaminergic neuronal death might involve defects in calcium regulatory proteins that control intracellular calcium homeostasis, and these could be corrected by inhibiting L-type VDCC activity. These findings support the notion that hypertensive patients who are on long-term intake of dihydropyridine have reduced risk for PD.