title: PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by a gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Ribosomal protein S3 (rpS3) has multiple functions related to protein synthesis, antioxidative activity, and UV endonuclease III activity. We have previously shown that PEP-1-rpS3 inhibits skin inflammation and provides neuroprotection against experimental cerebral ischemic damage. In this study, we examined whether PEP-1-rpS3 can protect DA neurons against oxidative stress in SH-SY5Y neuroblastoma cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-rpS3 was efficiently delivered to SH-SY5Y cells and the SN of the brain as confirmed by Western blot and immunohistochemical analysis. PEP-1-rpS3 significantly inhibited reactive oxygen species generation and DNA fragmentation induced by 1-methyl-4-phenylpyridinium, consequently leading to the survival of SH-SY5Y cells. The neuroprotection was related to the antiapoptotic activity of PEP-1-rpS3 that affected the levels of proapoptotic and antiapoptotic mediators. In addition, immunohistochemical data collected using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that PEP-1-rpS3 markedly protected DA cells in the SN against MPTP-induced oxidative stress. Therefore, our results suggest that PEP-1-rpS3 may be a potential therapy for PD.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Kim
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Woo
authors.forename: So Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000378:metabolism*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; C044152:ribosomal protein S3; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine