title: Transduced Tat-SAG fusion protein protects against oxidative stress and brain ischemic insult.
abstract: Reactive oxygen species (ROS) have been implicated in the pathogenesis of ischemic brain injury. Sensitive to apoptosis gene (SAG) is a RING-finger protein that exhibits antioxidant activity against a variety of redox reagents. However, the protective effect of SAG in brain ischemic injury is unclear. Here, we investigated the protective effects of a Tat-SAG fusion protein against cell death and ischemic insult. When Tat-SAG fusion protein was added to the culture medium of astrocytes, it rapidly entered the cells and protected them against oxidative stress-induced cell death. Immunohistochemical analysis revealed that, when Tat-SAG fusion protein was intraperitoneally injected into gerbils, wild-type Tat-SAG prevented neuronal cell death in the CA1 region of the hippocampus in response to transient forebrain ischemia. In addition, wild-type Tat-SAG fusion protein decreased lipid peroxidation in the brain compared with mutant Tat-SAG- or vehicle-treated animals. Our results demonstrate that Tat-SAG fusion protein is a tool for the treatment of ischemic insult and it can be used in protein therapy for various disorders related to ROS, including stroke.
authors.affiliation: Department of Biomedical Science, Research Institute for Bioscience and Biotechnology, Medical & Bio-material Research Center, Hallym University, Chunchon, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Min Seop
authors.initials: MS
authors.lastname: Jeong
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hoon Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: An
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Jang
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Kil Soo
authors.initials: KS
authors.lastname: Lee
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019610:Cytoprotection; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D005849:Gerbillinae; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress; D015202:Protein Engineering; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015696:Gene Products, tat; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases