H_2O_2诱导Neuro-2a细胞死亡机理的研究  

THE MECHANISM OF NEURO-2a CELL DEATH INDUCED BY H_2O_2

作　　者：张震[1] 杨巍[1] 朱山[1] 卢智刚[1] 翟中和[1] 

机构地区：[1]北京大学生命科学学院,北京100871

出　　处：《实验生物学报》2001年第1期35-43,共9页Acta Biologiae Experimentalis Sinica

基　　金：国家重点基础研究发展规划项目;No.G1999053905~~

摘　　要：细胞内线粒体呼吸链过程中的电子漏和神经细胞代谢的酶类如单胺氧化酶(MAO)等可产生活性氧物质(ROS)如H_2O_2等。ROS对细胞有毒性作用,导致细胞死亡,在许多疾病特别是神经退行性疾病中具有重要作用。我们用H_2o_2诱导N-2a神经母细胞瘤细胞,利用光镜、荧光显微镜、透射电镜观察了诱导的N-2a细胞的死亡,结果表明其死亡形式不同于典型的细胞凋亡,而类似于Ⅱ型神经细胞编程性死亡,死亡细胞染色质呈团块状凝集,细胞核膜仍保持完整。DNA不降解形成ladder,且不需要caspase-3,1的活性,但是H_2O_2诱导的Neuro-2a细胞死亡可以被Bcl-X_L,抑制。我们的结果可以说明,ROS介导的细胞毒性作用是导致Ⅱ型神经细胞编程性死亡的一个原因。Reactive oxygen species (ROS), such as H2O2, can be produced by enzymes involved in electron leakage of respiration chain in mitochondria, and by neurochemical enzymes such as monoamine oxidase in neural cells. ROS are toxic to cells, and can result in cell death. ROS also play an important role in some diseases, especially in neurodegenerative diseases by yet unknown mechanisms. In the current research, the N-2a neuroblastoma cell was treated with H2O2, and the morphological changes of cell death were characterized. Our results show that N-2a cell death is different from classical apoptosis, but belongs to type Ⅱ nerve cell programmed death, which shows condensed chromatin within intact nuclear envelope and no apoptolic body. The chromatin DNA of dead cells shows no internucleosomal cleavage, as well as no requirement for caspase-3, 1 activity. However, the H2O2-induced N-2a cell death can be inhibited by Bcl-XL. It can be concluded that type Ⅱ nerve cell death is the result of cell toxicity mediated by ROS. The results pave the way for further research of type Ⅱ nerve cell death.

关 键 词：神经细胞 H2O2 过氧化氢 Neuro-2a细胞 死亡机理 

分 类 号：Q42[生物学—神经生物学]