Kindy M S, Carney J P, Dempsey R J, Carney J M
Department of Biochemistry, University of Kentucky, Lexington 40536-0084.
J Mol Neurosci. 1991;2(4):217-28.
Cerebral ischemia and reperfusion results in an active series of metabolic events, eventually leading to cell death. The expression of specific genes during cerebral ischemia and reperfusion may play an important, determinant role in the mechanisms controlling cellular processes. Ten minutes of bilateral carotid occlusion in the Mongolian gerbil was found to increase the messenger RNA for both the c-fos and c-jun protooncogenes. The changes in gene expression were detected in the regions of ischemia, specifically the cortex and striatum, and no increases were seen in either the brain stem or the cerebellum, which possess a separate circulation. Induction of protooncogene mRNA is correlated to the duration of ischemia, i.e., the longer the time of ischemia, the greater the increase in c-fos expression. Pretreatment of animals with pentobarbital reduced the effect of the ischemic insult and prevented the increase in c-fos mRNA. Analysis of the c-fos and c-jun proteins after ischemia demonstrated an increase in the formation of a functional transcriptional complex and association with the AP-1 binding region. These findings suggest that ischemic cell death and recovery in neurodegenerative disorders such as stroke may involve the regulated expression of these protooncogenes early in the pathway of ischemia.
脑缺血再灌注会引发一系列活跃的代谢事件，最终导致细胞死亡。脑缺血再灌注期间特定基因的表达可能在控制细胞进程的机制中发挥重要的决定性作用。研究发现，蒙古沙鼠双侧颈动脉闭塞10分钟会使原癌基因c-fos和c-jun的信使核糖核酸增加。基因表达的变化在缺血区域，特别是皮质和纹状体中被检测到，而在具有独立血液循环的脑干或小脑中未观察到增加。原癌基因信使核糖核酸的诱导与缺血持续时间相关，即缺血时间越长，c-fos表达增加得越多。用戊巴比妥预处理动物可减轻缺血损伤的影响并阻止c-fos信使核糖核酸的增加。缺血后对c-fos和c-jun蛋白的分析表明，功能性转录复合物的形成增加并与AP-1结合区域相关联。这些发现表明，在中风等神经退行性疾病中，缺血性细胞死亡和恢复可能在缺血途径早期涉及这些原癌基因的调控表达。
