The roles of the thioredoxin system and peroxiredoxins in 1-methyl-4-phenyl-pyridinium ion-induced cytotoxicity in rat pheochromocytoma cells.

The 1-methyl-4-phenyl-pyridinium ion (MPP(+)), an active metabolite of the neurotoxin, N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), induces death in rat pheochromocytoma (PC12) cells, suggesting a cell model of Parkinson's disease (PD). However, most of the toxic mechanisms remain illusive. In this study, we have found that MPP(+) induced apoptotic cell death in PC12 cells as measured by the MTT assay and annexin V-FITC staining. Besides, MPP(+) also resulted in decreased mitochondrial membrane potential and increased mitochondrial free radical formation as imaged by the staining of TMRE or MitoSOX, respectively, confirming the neurotoxic effect of MPP(+) by interfering with mitochondrial functions. Western blot analysis indicated that MPP(+) differentially regulated the expressions and over-oxidation of thioredoxin systems and peroxiredoxins. Since these enzymes are known to prevent oxidative stress and apoptosis, these evidences could be regarded as a novel neurotoxic mechanism of MPP(+) and also provide an alternative view of developing drug therapies for PD.
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