González-García M, García I, Ding L, O'Shea S, Boise L H, Thompson C B, Núñez G
Department of Pathology and Anatomy, University of Michigan Medical School, Ann Arbor 48109, USA.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4304-8. doi: 10.1073/pnas.92.10.4304.
Previous studies have implicated the bcl-2 protooncogene as a potential regulator of neuronal survival. However, mice lacking functional bcl-2 exhibited normal development and maintenance of the central nervous system (CNS). Since bcl-2 appears dispensable for neuronal survival, we have examined the expression and function of bcl-x, another member of the bcl-2 family of death regulatory genes. Bcl-2 is expressed in neuronal tissues during embryonic development but is down-regulated in the adult CNS. In contrast, Bcl-xL expression is retained in neurons of the adult CNS. Two different forms of bcl-x mRNA and their corresponding products, Bcl-xL and Bcl-x beta, were expressed in embryonic and adult neurons of the CNS. Microinjection of bcl-xL and bcl-x beta cDNAs into primary sympathetic neurons inhibited their death induced by nerve growth factor withdrawal. Thus, Bcl-x proteins appear to play an important role in the regulation of neuronal survival in the adult CNS.
以往的研究表明，bcl-2原癌基因是神经元存活的潜在调节因子。然而，缺乏功能性bcl-2的小鼠中枢神经系统（CNS）发育和维持正常。由于bcl-2对于神经元存活似乎并非必需，我们研究了bcl-2死亡调节基因家族的另一个成员bcl-x的表达和功能。bcl-2在胚胎发育期间的神经组织中表达，但在成年中枢神经系统中表达下调。相比之下，Bcl-xL在成年中枢神经系统的神经元中持续表达。两种不同形式的bcl-x mRNA及其相应产物Bcl-xL和Bcl-xβ在中枢神经系统的胚胎和成年神经元中表达。将bcl-xL和bcl-xβ cDNA显微注射到原代交感神经元中可抑制因神经生长因子撤除诱导的细胞死亡。因此，Bcl-x蛋白似乎在成年中枢神经系统神经元存活的调节中发挥重要作用。
