Dempsey R J, Carney J M, Kindy M S
University of Kentucky Medical Center, Lexington.
Acta Neurochir Suppl (Wien). 1990;51:189-91. doi: 10.1007/978-3-7091-9115-6_64.
Ornithine Decarboxylase (ODC) is the rat controlling enzyme of polyamine biosynthesis and has been shown to be produced in a delayed fashion in response to cerebral ischaemia. Its appearance has been linked to the development of vasogenic brain oedema. To understand the genetic control of this protein, Mongolian gerbils were studied for the possible expression of the ODC gene as compared to that of the inducible proto oncogenes c-fos and c-jun after transient bilateral carotid artery occlusion. Total cellular RNA was isolated from gerbil brains by guanidine-thiocyanate extraction and characterized by northern blot analysis for c-fos, c-jun, and ODC mRNA over reperfusion times. c-fos and c-jun expression rose rapidly with peak level reached at 60 min of reperfusion (70 x control, p less than or equal to 0.01). Peak levels of ODC mRNA induction were seen at 4 hrs reperfusion (2.83 x control, p less than or equal to 0.01) consistent with the period of maximum of brain oedema as measured by specific gravity (1.0386 +/- 0.0009, p less than or equal to 0.05). These data indicate the differential timing of genetic expression during the reperfusion period after transient ischaemia. Such studies suggest that potential therapies may be possible by addressing the delayed ODC component of ischaemic oedema formation and allow a greater understanding of the role of gene induction in the multifaceted cerebral response to ischaemia.
鸟氨酸脱羧酶(ODC)是多胺生物合成的关键调控酶,已证明其在脑缺血后以延迟方式产生。它的出现与血管源性脑水肿的发展有关。为了解该蛋白的基因调控,研究了蒙古沙鼠在短暂双侧颈动脉闭塞后ODC基因与诱导型原癌基因c-fos和c-jun相比的可能表达情况。通过硫氰酸胍提取从沙鼠脑分离总细胞RNA,并通过Northern印迹分析在再灌注期间对c-fos、c-jun和ODC mRNA进行鉴定。c-fos和c-jun表达迅速上升,在再灌注60分钟时达到峰值水平(70倍于对照,p≤0.01)。ODC mRNA诱导的峰值水平在再灌注4小时时出现(2.83倍于对照,p≤0.01),这与通过比重测量的脑水肿最大值时期一致(1.0386±0.0009,p≤0.05)。这些数据表明短暂缺血后再灌注期间基因表达的时间差异。此类研究表明,通过针对缺血性水肿形成中延迟的ODC成分进行潜在治疗可能是可行的,并有助于更深入了解基因诱导在大脑对缺血的多方面反应中的作用。