PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson’s disease mouse model

BMB Reports

Sung Yeon Park^1¹  †, Dae Won Kim^2²  Eun Ji Yeo^1³  Jong Kyu Youn^1⁴  †, Seung Tae Kim^1⁵ 

[1] Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090^4;Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702^2;Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea^5;Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702^1;Department of Pediatrics, Hallym University Medical Center, Pyungchon 431-796^3

关键词: Dopaminergic neuron;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

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.

【 授权许可】

Unknown