Bax promotes neuronal cell death and is downregulated during the development of the nervous system.
Bax promotes neuronal cell death and is downregulated during the development of the nervous system.
复制标题
DOI：
--
复制
发表时间：
1997-03
期刊：
影响因子：
4.6
通讯作者：
K. Vekrellis;M. J. McCarthy;A. Watson;J. Whitfield;L. Rubin;J. Ham
中科院分区：
文献类型：
--
作者：
K. Vekrellis;M. J. McCarthy;A. Watson;J. Whitfield;L. Rubin;J. Ham
Bcl2和Bclx蛋白抑制细胞程序性死亡，而Bax促进细胞凋亡。我们研究了Bcl2、Bax和Bclx在神经元分化发育过程中的表达规律。这三种蛋白在新生大鼠中都有广泛的表达，但在成年大鼠的大脑皮层、小脑和心肌中，Bax的水平降低了20到140倍，而在所研究的任何组织中，Bclx的表达都没有下调。在大脑皮层和小脑中，Bax水平的下降发生在发育细胞死亡之后。此外，向依赖神经生长因子存活的培养的交感神经细胞内微量注射Bax表达载体，可在存活因子存在的情况下诱导细胞凋亡，并增加神经生长因子停用后的细胞死亡率。这种作用可以通过共同注射Bclxl或杆状病毒p35蛋白的表达载体来阻断，P35蛋白是半胱氨酸天冬氨酸酶(ICE样蛋白)的抑制物。这些结果表明，在发育过程中，神经元对诱导凋亡信号的敏感性可能通过调节Bax水平来调节，Bax诱导的死亡需要caspase活性。
The Bcl-2 and Bcl-x proteins suppress programmed cell death, whereas Bax promotes apoptosis. We investigated the pattern of expression of Bcl-2, Bax and Bcl-x during neuronal differentiation and development. All three proteins were widely expressed in neonatal rats but, in the adult, Bax levels were 20- to 140-fold lower in the cerebral cortex, cerebellum and heart muscle, whereas Bcl-x was not downregulated in any of the tissues examined. In the cerebral cortex and cerebellum, the decrease in Bax levels occurred after the period of developmental cell death. Further, microinjection of a Bax expression vector into cultured sympathetic neurons, which depend on nerve growth factor for survival, induced apoptosis in the presence of survival factor and increased the rate of cell death after nerve growth factor withdrawal. This effect could be blocked by co-injection of an expression vector for Bcl-xL or for the baculovirus p35 protein, an inhibitor of caspases (ICE-like proteases). These results suggest that, during development, the sensitivity of neurons to signals that induce apoptosis may be regulated by modulating Bax levels and that Bax-induced death requires caspase activity.