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

Abstract

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.

• Authors: Jong Kyu Youn, Dae Won Kim, Seung Tae Kim, Sung Yeon Park, Eun Ji Yeo, Yeon Joo Choi, Hae-Ran Lee, Duk-Soo Kim, Sung-Woo Cho, Kyu Hyung Han, Jinseu Park, Won Sik Eum, Hyun Sook Hwang, Soo Young Choi
• Journal: BMB reports (BMB Rep) Vol. 47 Issue 10 Pg. 569-74 (Oct 2014) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 24499676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Heme Oxygenase-1
• PEP-1-heme oxygenase-1 fusion protein

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Cell Death (drug effects)
• Cell Line, Tumor
• Disease Models, Animal
• Dopaminergic Neurons (drug effects, pathology)
• Heme Oxygenase-1 (pharmacology, therapeutic use)
• Humans
• Male
• Mice, Inbred C57BL
• Nerve Degeneration (complications, pathology, prevention & control)
• Parkinson Disease (complications, drug therapy, pathology)
• Recombinant Fusion Proteins (pharmacology, therapeutic use)
• Substantia Nigra (drug effects, pathology)
• Time Factors
• Transduction, Genetic