title: PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax expression.
abstract: P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a tumor suppressor protein and plays a key cell survival role in a variety of human cancers. Under pathophysiological conditions, the INK4 group proteins participate in novel biological functions associated with neuronal diseases and oxidative stress. Parkinson's disease (PD) is characterized by loss of dopaminergic neurons, and oxidative stress is important in its pathogenesis. Therefore, we examined the effects of PEP-1-p18 on oxidative stress-induced SH-SY5Y cells and in a PD mouse model. The transduced PEP-1-p18 markedly inhibited 1-methyl-4-phenyl pyridinium-induced SH-SY5Y cell death by inhibiting Bax expression levels and DNA fragmentation. Additionally, PEP-1-p18 prevented dopaminergic neuronal cell death in the substantia nigra of a 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced PD mouse model. These results indicate that PEP-1-p18 may be a useful therapeutic agent against various diseases and is a potential tool for treating PD.
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Eom
authors.forename: Ga Hyeon
authors.initials: GH
authors.lastname: Yoon
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Cho
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020267:MPTP Poisoning; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C503924:Pep-1 peptide; D010455:Peptides; D051028:bcl-2-Associated X Protein; D003543:Cysteamine