In vivo delivery of a XIAP (BIR3-RING) fusion protein containing the protein transduction domain protects against neuronal death induced by seizures.
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 TUNEL positive cells and increase the number of surviving cells in the ipsilateral CA3 subfield of the hippocampus at 24 h 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.
Li
Tianfu
T
Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, 200040 Shanghai, China.
Fan
Yongfeng
Y
Luo
Yumin
Y
Xiao
Baoguo
B
Lu
Chuanzhen
C
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D014161:Transduction, Genetic / Q000379:methods; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000008:administration & dosage* / Q000737:chemistry
D018690:Excitatory Amino Acid Agonists; D011993:Recombinant Fusion Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D004281:Docosahexaenoic Acids; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D007608:Kainic Acid