Abstract
Thioredoxin (TRX) is a redox-active protein which plays a cytoprotective role against oxidative stress. Geranylgeranylacetone (GGA), used widely as an anti-ulcer drug, has been reported to induce TRX as well as heat shock protein 70 (HSP70) in hepatocytes and other cells. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes dopaminergic denervation and Parkinsonism in humans. The 1-methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of MPTP, induces cell death in a rat pheochromocytoma cell line (PC12 cells). We found that MPP(+) suppresses TRX expression in PC12 cells. Overexpression or administration of TRX attenuates MPP(+)-induced neurotoxicity on PC12 cells. Moreover, GGA induces expression of TRX and HSP70 and attenuates MPP(+)-induced toxicity in PC12 cells. These results indicate that TRX and GGA have a possible potential as new therapeutic agents for Parkinson disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenylpyridinium / antagonists & inhibitors*
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Animals
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Anti-Ulcer Agents / pharmacology*
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Cell Survival / drug effects
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Cell Survival / physiology
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Diterpenes / pharmacology*
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Dose-Response Relationship, Drug
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Drug Interactions / physiology
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HSP70 Heat-Shock Proteins / drug effects
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HSP70 Heat-Shock Proteins / metabolism
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L-Lactate Dehydrogenase / drug effects
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L-Lactate Dehydrogenase / metabolism
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Neurons / drug effects*
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Neurons / metabolism
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Neurotoxins / antagonists & inhibitors*
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Oxidative Stress / drug effects*
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Oxidative Stress / physiology
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PC12 Cells
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Rats
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Thioredoxins / pharmacology*
Substances
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Anti-Ulcer Agents
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Diterpenes
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HSP70 Heat-Shock Proteins
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Neurotoxins
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Thioredoxins
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L-Lactate Dehydrogenase
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1-Methyl-4-phenylpyridinium
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geranylgeranylacetone