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

Victor T K Chen, Chuen Lin Huang, Yi Chao Lee, Wei Chen Liao, Nai Kuei Huang

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1577-1583
頁數7
期刊Toxicology in Vitro
24
發行號6
DOIs
出版狀態已發佈 - 九月 2010
對外發佈Yes

ASJC Scopus subject areas

  • Toxicology

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