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KMID : 0624620140470100569
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BMB Reports
2014 Volume.47 No. 10 p.569 ~ p.574
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PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson’s disease mouse model
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Youn Jong-Kyu
Kim Dae-Won
Kim Seung-Tae
Park Sung-Yeon
Yeo Eun-Ji
Choi Yeon-Joo
Lee Hae-Ran
Kim Duk-Soo
Cho Sung-Woo
Han Kyu-Hyung
Park Jin-Seu
Eum Won-Sik
Hwang Hyun-Sook
Choi Soo-Young
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Abstract
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Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and Fe2+, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson’s disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion (MPP+). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce MPP+-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.
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KEYWORD
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Dopaminergic neuron, Heme oxygenase-1, MPTP, Parkinson’s disease, Protein transduction domain
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