Antonawich F J, Krajewski S, Reed J C, Davis J N
Department of Neurology and Program in Neurobiology, State University of New York at Stony Brook, 11794-8121, USA.
J Cereb Blood Flow Metab. 1998 Aug;18(8):882-6. doi: 10.1097/00004647-199808000-00008.
Five minutes of bilateral common carotid artery occlusion in the Mongolian gerbil results in a selective, delayed death of CA1 pyramidal neurons. Although Bcl-2 appears to protect a variety of cells from cell death, the precise role of this apoptosis-regulating protein is complicated. We used immunoblots to estimate levels of Bcl-2, Bcl-x(l), and Bax at various times after carotid occlusion. Rather than Bcl-2, Bcl-x(l) appears to be the predominant neuroprotective form of this family of proto-oncogenes in the gerbil hippocampus. After transient ischemia, Bcl-2 and Bcl-x(l) protein levels remained the same. However, Bax levels were dramatically increased at 6 hours after ischemia, compared with sham-operated animals, and were still elevated at 72 hours after ischemia. To monitor dimerization interactions among theses apoptosis-regulating molecules, immunoprecipitation studies were conducted. These studies demonstrated that Bcl-x(l) association with Bax increases after ischemia. Therefore, Bax may disrupt the more favorable Bcl-x(l) (Bcl-2) interactions necessary for normal neuronal functioning and thus promote transient ischemic death.
在蒙古沙鼠中，双侧颈总动脉闭塞5分钟会导致CA1锥体神经元选择性延迟死亡。虽然Bcl-2似乎能保护多种细胞免于死亡，但这种凋亡调节蛋白的确切作用很复杂。我们使用免疫印迹法来估计颈动脉闭塞后不同时间的Bcl-2、Bcl-x(l)和Bax水平。在沙鼠海马体中，Bcl-x(l)而非Bcl-2似乎是这个原癌基因家族的主要神经保护形式。短暂性脑缺血后，Bcl-2和Bcl-x(l)蛋白水平保持不变。然而，与假手术动物相比，缺血6小时后Bax水平显著升高，且在缺血72小时后仍升高。为监测这些凋亡调节分子之间的二聚化相互作用，进行了免疫沉淀研究。这些研究表明，缺血后Bcl-x(l)与Bax的结合增加。因此，Bax可能会破坏正常神经元功能所需的更有利的Bcl-x(l)（Bcl-2）相互作用，从而促进短暂性缺血性死亡。
