Transduced Tat-SAG fusion protein protects against oxidative stress and brain ischemic insult.
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.
Kim
Dae Won
DW
Department of Biomedical Science, Research Institute for Bioscience and Biotechnology, Medical & Bio-material Research Center, Hallym University, Chunchon, Korea.
Lee
Sun Hwa
SH
Jeong
Min Seop
MS
Sohn
Eun Jeong
EJ
Kim
Mi Jin
MJ
Jeong
Hoon Jae
HJ
An
Jae Jin
JJ
Jang
Sang Ho
SH
Won
Moo Ho
MH
Hwang
In Koo
IK
Cho
Sung-Woo
SW
Kang
Tae-Cheon
TC
Lee
Kil Soo
KS
Park
Jinseu
J
Yoo
Ki-Yeon
KY
Eum
Won Sik
WS
Choi
Soo Young
SY
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*
D015696:Gene Products, tat; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases