The expression of Smac and XIAP in rat hippocampus following limbic seizure induced by kainic acid injection into amygdaloid nucleus
- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 2
- DOI:
- 10.3321/j.issn:0371-0874.2004.02.008
- Key Word:
- 红藻氨酸;癫痫;海马;凋亡;半胱天冬蛋白酶-9;第二个线粒体源的半胱天冬蛋白酶激活物/直接与凋亡抑制蛋白结合的低等电点蛋白;X染色体连锁的凋亡抑制蛋白
Abstract： 应用红藻氨酸(kainic acid,KA)诱导的大鼠边缘叶癫痫发作模型,检测第二个线粒体源的半胱天冬蛋白酶激活物/直接与凋亡抑制蛋白结合的低等电点蛋白(secondmitochondrial activatorofcaspases/directinhibitorofapoptosisprotein-bindingproteinoflowisoelectric point[PI],Smac/DIABLO)和X染色体连锁的凋亡抑制蛋白(X-chromosome-linkedinhibitor of apoptosis protein,XIAP)在癫痫大鼠海马神经元表达.单侧杏仁核内注射KA诱导癫痫发作,1 h后用安定终止发作,然后分别用TUNEL染色和cresyl violet染色观察海马神经元存活和凋亡的变化,用免疫荧光和Western blot检测海马Smac/DIABLO、XIAP和半胱天冬蛋白酶-9(caspase-9)的表达.结果表明,发作终止2 h时KA注射同侧海马CA3区细胞浆内Smac/DIABLO蛋白表达增加,4h时caspase-9出现裂解片断,8 h时出现TUNEL阳性细胞,24 h时达高峰.脑室内注射caspase-9抑制剂z-LEHD-fluoromethylketone(z-LEHD-fmk)可减少TUNEL阳性细胞,增加存活神经元.发作后KA注射同侧海马CA3区神经元caspase-9免疫反应性增强,Smac/DIABLO和XIAP弥散于整个神经元内.对侧海马未检测到TUNEL阳性细胞及Smac/DIABLO和XIAP蛋白的上述变化.以上结果提示,癫痫发作可诱导Smac/DIABLO蛋白从线粒体向细胞浆的移位、XIAP亚细胞分布改变和caspase-9的激活,Smac/DIABLO、XIAP和caspase-9可能参与了癫痫神经元损伤的病理生理机制,caspase-9可能是潜在的治疗靶点.
- [1]S J, Riedl,M, Renatus,R, Schwarzenbacher,etc.Structural basis for the inhibition of caspase-3 by XIAP.[J].2001,104(5).
- [2]Henshall DC,Simon RP,Chen J.Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizures.[J].2000,74(3).
- [3]McIntyre DC,Fong WG,Xu D,etc.Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus.[J].1999,19(12).
- [4]S M, Srinivasula,R, Hegde,A, Saleh,etc.A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.[J].2001,410(6824).
- [5]Bonislawski DP,Skradski SL,Schindler CK,etc.Formation of the Apaf-1/cytochrome c complex precedes activation of caspase-9 during seizure-induced neuronal death.[J].2001,8(12).
- [6]Lotocki G,Dietrich WD,Frydel B,etc.Monoubiquitination and Cellular Distribution of XIAP in Neurons after Traumatic Brain Injury.[J].2003,23(10).
- [7]Tiekoter KL,Henshall DC,Lan JQ,etc.Activation of Bcl-2-associated death protein and counter-response of Akt within cell populations during seizure-induced neuronal death.[J].2002,22(19).
- [8]Chan PH,Hayashi T,Ferrand Drake M,etc.Interaction between XIAP and Smac/DIABLO in the mouse brain after transient focal cerebral ischemia.[J].2003,23(9).
- [9]L, Zhang,J, Yu,B H, Park,etc.Role of BAX in the apoptotic response to anticancer agents.[J].2000,290(5493).