Transduced Tat-SOD fusion protein protects against ischemic brain injury.

Abstract

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.

• Authors: Dae Won Kim, Won Sik Eum, Sang Ho Jang, So Young Kim, Hee Soon Choi, Soo Hyun Choi, Jae Jin An, Sun Hwa Lee, Kil Soo Lee, Kyuhyung Han, Tae-Cheon Kang, Moo Ho Won, Jung Hoon Kang, Oh-Shin Kwon, Sung-Woo Cho, Tae Yoon Kim, Jinseu Park, Soo Young Choi
• Journal: Molecules and cells (Mol Cells) Vol. 19 Issue 1 Pg. 88-96 (Feb 28 2005) ISSN: 1016-8478 [Print] United States
• PMID: 15750345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Antioxidants
• Gene Products, tat
• Recombinant Fusion Proteins
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (therapeutic use)
• Astrocytes (cytology, drug effects)
• Cell Death (drug effects)
• Gene Products, tat (therapeutic use)
• Gerbillinae
• Ischemic Attack, Transient (drug therapy)
• Male
• Mice
• Mice, Inbred ICR
• Oxidative Stress (physiology)
• Recombinant Fusion Proteins (therapeutic use)
• Reperfusion Injury (prevention & control)
• Superoxide Dismutase (therapeutic use)
• Transduction, Genetic