title: Tat-fused recombinant human SAG prevents dopaminergic neurodegeneration in a MPTP-induced Parkinson's disease model.
abstract: Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson's disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium (MPP(+)) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by MPP(+) in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Han
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; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D059290:Dopaminergic Neurons / Q000473:pathology*; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015696:Gene Products, tat; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases