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A possible role for an anti-apoptotic protein, survivin, in survival of neurons in the brain

抗凋亡蛋白生存素在大脑神经元存活中的可能作用

基本信息

批准号：
14580750
负责人：
OHSAWA Ikuroh
金额：
$ 2.18万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Precise mechanism for survival of neurons in central nervous system remains to be elucidated. It includes many anti-apoptotic proteins. Survivin is a member of the inhibitor-of-apoptosis protein. Its expression is determined in the developing embryo and in rapidly dividing cells including many human cancers. Previous studies demonstrated that survivin is expressed at G2/M in a cell-cycle dependent manner and associated with kinetochores of metaphase chromosomes and the central spindle midzone at anaphase, suggesting that survivin participates as a chromosomal passenger protein in cleavage furrow formation. Forced expression of survivin counteracted cell death induced by various apoptotic stimuli, whereas interference with the expression or function of survivin by a dominant negative form or antisense of survivin caused spontaneous apoptosis and multiple cell division defects, suggesting that survivin acts both as a mitotic regulator and as a cytoprotective factor at cell division. Then … More , we prepared polyclonal anti-survivin serum to investigate the expression of survivin in central nervous system. At first, we stained primary cultured cells derived from neocortex in rat embryo and found that survivin was expressed in MAP2 positive differentiated neurons. The expression was also observed in a part of astrocytes. Immunological staining of mouse brain section confirmed the expression of survivin in neurons. These results suggested that survivin might be included in anti-apoptotic machineries of differentiated neurons. On the other hand, we examined whether survivin expression in human gliomas would be a correlative of prognosis, and found that higher expression of survivin was correlated with the survival of gliomas. Thus, immunostaining of glioma with anti-survivin serum would be a powerful tool for a clinical prognosis. We also investigated whether urine surviving is useful for diagnosing bladder cancer, and found that ELISA system for survivin might be a useful tumor marker. Less

中枢神经系统神经元存活的确切机制仍有待阐明。它包括许多抗凋亡蛋白。Survivin是凋亡相关蛋白的一员。它的表达在发育中的胚胎和快速分裂的细胞中确定，包括许多人类癌症。以往的研究表明，生存素表达在G2/M的细胞周期依赖的方式，并与中期染色体的着丝粒和中央纺锤体中区在后期，这表明生存素参与作为一个染色体乘客蛋白在卵裂沟的形成。生存素的强制表达抵消了由各种凋亡刺激诱导的细胞死亡，而生存素的显性负性形式或反义干扰生存素的表达或功能引起自发性凋亡和多个细胞分裂缺陷，这表明生存素既作为有丝分裂调节因子，又作为细胞分裂时的细胞保护因子。然后 ...更多信息本研究制备了Survivin多克隆抗血清，以研究Survivin在中枢神经系统中的表达。我们首先对原代培养的大鼠胚胎大脑皮层细胞进行染色，发现Survivin在MAP 2阳性的分化神经元中表达。在部分星形胶质细胞中也有表达。小鼠脑切片免疫组化染色证实了Survivin在神经元中的表达。这些结果表明，生存素可能包括在分化的神经元的抗凋亡机制。另一方面，我们研究了生存素在人脑胶质瘤中的表达是否与预后相关，发现生存素的高表达与胶质瘤的生存相关。因此，用抗存活素血清对胶质瘤进行免疫染色将是临床预后的有力工具。我们还研究了尿Survivin对膀胱癌的诊断价值，发现ELISA检测Survivin可能是一种有用的肿瘤标志物。少