Journal
EXPERIMENTAL NEUROLOGY
Volume 197, Issue 2, Pages 301-308Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2005.08.021
Keywords
X-linked inhibitor of apoptosis protein; apoptosis; caspase; kainic acid; seizures
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The prevention of cell apoptosis is a promising strategy for neuroprotection against brain injury in seizures. X-linked inhibitor of apoptosis protein (XIAP) is regarded as the most potent inhibitor of cell apoptosis. In the present study, we fused the protein transduction domain (PTD) of Antennapedia Homeodomain of Drosophila (AntpHD) to XIAP (BIR3-RING) and explored the neuroprotective effect of XIAP in rats with seizures induced by kainic acid (KA). KA triggered neuronal death in the ipsilateral CA3 subfield of the hippocampus and activation of caspase-3 and -9. PTD-XIAP fusion protein can be delivered into cos7 cells in vitro. We used intraperitoneal injection to deliver the PTD-XIAP fusion protein which can enter into brain, significantly decrease the TLYNEL positive cells and increase the number Of Surviving cells in the ipsilateral CA3 subfield of the hippocampus at 24 In after KA-induced seizures. Furthermore, PTD-XIAP fusion protein attenuated activated caspase-3 and -9. These results demonstrate the neuroprotective effect of PTD-XIAP fusion protein against brain injury possibly through the inhibition of caspase. The significance of these findings in the treatment of epilepsy still needs to be extensively studied. (c) 2005 Elsevier Inc. All rights reserved.
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