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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1577-1583
Number of pages7
JournalToxicology in Vitro
Volume24
Issue number6
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Fingerprint

1-Methyl-4-phenylpyridinium
Peroxiredoxins
Thioredoxins
PC12 Cells
Pheochromocytoma
Cytotoxicity
Parkinson Disease
Rats
Ions
Staining and Labeling
Drug therapy
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Oxidative stress
Fluorescein-5-isothiocyanate
Mitochondrial Membrane Potential
Poisons
Annexin A5
Neurotoxins
Cell death
Metabolites

Keywords

  • 1-Methyl-4-phenyl-pyridinium ion
  • Peroxiredoxin
  • Thioredoxin
  • Thioredoxin reductase

ASJC Scopus subject areas

  • Toxicology

Cite this

The roles of the thioredoxin system and peroxiredoxins in 1-methyl-4-phenyl-pyridinium ion-induced cytotoxicity in rat pheochromocytoma cells. / Chen, Victor T K; Huang, Chuen Lin; Lee, Yi Chao; Liao, Wei Chen; Huang, Nai Kuei.

In: Toxicology in Vitro, Vol. 24, No. 6, 09.2010, p. 1577-1583.

Research output: Contribution to journalArticle

Chen, Victor T K ; Huang, Chuen Lin ; Lee, Yi Chao ; Liao, Wei Chen ; Huang, Nai Kuei. / The roles of the thioredoxin system and peroxiredoxins in 1-methyl-4-phenyl-pyridinium ion-induced cytotoxicity in rat pheochromocytoma cells. In: Toxicology in Vitro. 2010 ; Vol. 24, No. 6. pp. 1577-1583.
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