Transduced Tat-SOD fusion protein protects against ischemic brain injury.
Reactive oxygen species (ROS) are implicated in reperfusion injury after transient focal cerebral ischemia. The antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD), is one of the major means by which cells counteract the deleterious effects of ROS after ischemia. Recently, we reported that when Tat-SOD fusion protein is transduced into pancreatic beta cells it protects the beta cells from destruction by relieving oxidative stress in ROS-implicated diabetes (Eum et al., 2004). In the present study, we investigated the protective effects of Tat-SOD fusion protein against neuronal cell death and ischemic insults. When Tat-SOD was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Immunohistochemical analysis revealed that Tat-SOD injected intraperitoneally (i.p.) into mice has access to various tissues including brain neurons. When i.p. injected into gerbils, Tat-SOD prevented neuronal cell death in the hippocampus in response to transient fore-brain ischemia. These results suggest that Tat-SOD provides a strategy for therapeutic delivery in various hu-man diseases, including stroke, related to this anti-oxidant enzyme or to ROS.
Kim
Dae Won
DW
Department of Genetic Engineering and Research, Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
Eum
Won Sik
WS
Jang
Sang Ho
SH
Kim
So Young
SY
Choi
Hee Soon
HS
Choi
Soo Hyun
SH
An
Jae Jin
JJ
Lee
Sun Hwa
SH
Lee
Kil Soo
KS
Han
Kyuhyung
K
Kang
Tae-Cheon
TC
Won
Moo Ho
MH
Kang
Jung Hoon
JH
Kwon
Oh-Shin
OS
Cho
Sung-Woo
SW
Kim
Tae Yoon
TY
Park
Jinseu
J
Choi
Soo Young
SY
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D015696:Gene Products, tat / Q000627:therapeutic use; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D014161:Transduction, Genetic
D000975:Antioxidants; D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase