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

中枢神经系统神经元存活的确切机制尚不清楚。它含有许多抗细胞凋亡的蛋白质。Survivin是细胞凋亡抑制蛋白的一员。它的表达是在发育中的胚胎和快速分裂的细胞中决定的，包括许多人类癌症。以往的研究表明，Survivin在G2/M期以细胞周期依赖的方式表达，并与中期染色体的着丝点和后期的中央纺锤体中间区相关，这表明Survivin作为染色体乘客蛋白参与了卵裂沟的形成。Survivin的强制表达可拮抗各种凋亡刺激诱导的细胞死亡，而以显性负性形式或反义Survivin干扰Survivin的表达或功能可导致自发性细胞凋亡和多种细胞分裂缺陷，提示Survivin在细胞分裂过程中既是有丝分裂调节因子，又是细胞保护因子。然后是…此外，我们还制备了Survivin多克隆抗血清，以研究Survivin在中枢神经系统中的表达。首先，我们对大鼠胚胎新皮质来源的原代培养细胞进行了染色，发现Survivin在MAP2阳性分化神经元中有表达。在部分星形胶质细胞中也观察到了这种表达。小鼠脑切片免疫染色证实Survivin在神经元中有表达。这些结果提示，Survivin可能参与了分化神经元的抗凋亡机制。另一方面，我们检测了Survivin在人脑胶质瘤中的表达是否与预后相关，发现Survivin的高表达与胶质瘤的生存相关。因此，用Survivin抗血清对胶质瘤进行免疫染色将是判断临床预后的有力工具。我们还研究了尿液存活是否有助于膀胱癌的诊断，并发现检测Survivin的ELISA系统可能是一种有用的肿瘤标志物。较少

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