PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson's disease mouse model.
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.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Jong Kyu
JK
Youn
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702, Korea.
Dae Won
DW
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Seung Tae
ST
Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Sung Yeon
SY
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Eun Ji
EJ
Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Yeon Joo
YJ
Choi
Department of Pediatrics, Hallym University Medical Center, Pyungchon 431-796, Korea.
Hae-Ran
HR
Lee
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
Duk-Soo
DS
Kim
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Sung-Woo
SW
Cho
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Kyu Hyung
KH
Han
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Jinseu
J
Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Won Sik
WS
Eum
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Hyun Sook
HS
Hwang
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
Soo Young
SY
Choi
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D051547:Heme Oxygenase-1 / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014161:Transduction, Genetic
D011993:Recombinant Fusion Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D051547:Heme Oxygenase-1; C561500:PEP-1-heme oxygenase-1 fusion protein