Thioredoxin suppresses 1-methyl-4-phenylpyridinium-induced neurotoxicity in rat PC12 cells |
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Authors: | Bai Jie Nakamura Hajime Hattori Itaro Tanito Masaki Yodoi Junji |
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Institution: | Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan. |
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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. |
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