Cimarosti Helena, Jones Nicole M, O'Shea Ross D, Pow David V, Salbego Christianne, Beart Philip M
Howard Florey Institute, University of Melbourne, Victoria 3010, Australia; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurosci Lett. 2005 Sep 2;385(1):52-7. doi: 10.1016/j.neulet.2005.05.006.
Exposure of the brain to a sublethal insult can protect against a subsequent brain injury. Hypoxic preconditioning induces tolerance to hypoxic--ischemic injury in neonatal rat brain and is associated with changes in gene and protein expression. To study the involvement of excitatory amino acid transporters (EAAT1 and EAAT2) and estrogen receptors (ERalpha and ERbeta) in neonatal hypoxia--induced ischemic tolerance, we examined changes in expression of these proteins in the cortex, hippocampus and striatum of newborn rats at different time points after exposure to sublethal hypoxia (8% O(2), 3h). Preconditioning with hypoxia 24h before hypoxia-ischemia afforded marked brain protection compared with littermate control animals as determined by morphological assessment. Immunoblot analysis showed that EAAT2 and ERalpha were significantly increased by 55% and 49%, respectively, in cortex at 24h after hypoxic-preconditioning. Surprisingly, at the same time point, a significant decrease of EAAT2 by 48% in striatum was observed. In contrast, hypoxic preconditioning had no effect on the levels of EAAT1 and ERbeta in any of the brain regions studied at any of the time points analyzed. The similar pattern of changes in EAAT2 and ERalpha levels suggests that ERalpha might interact with EAAT2 in producing preconditioning. The endogenous molecular mechanisms modulated by hypoxia preconditioning may contribute to the development of hypoxia-induced ischemic tolerance, and may provide novel therapeutic targets for the treatment of cerebral ischemia.
大脑暴露于亚致死性损伤可对随后的脑损伤起到保护作用。缺氧预处理可诱导新生大鼠脑对缺氧缺血性损伤产生耐受性，并与基因和蛋白质表达的变化有关。为了研究兴奋性氨基酸转运体（EAAT1和EAAT2）和雌激素受体（ERα和ERβ）在新生大鼠缺氧诱导的缺血耐受性中的作用，我们检测了在暴露于亚致死性缺氧（8% O₂，3小时）后不同时间点，新生大鼠皮质、海马和纹状体中这些蛋白质的表达变化。通过形态学评估确定，与同窝对照动物相比，在缺氧缺血前24小时进行缺氧预处理可提供显著的脑保护。免疫印迹分析显示，缺氧预处理后24小时，皮质中EAAT2和ERα分别显著增加55%和49%。令人惊讶的是，在同一时间点，纹状体中EAAT2显著降低48%。相比之下，在任何分析的时间点，缺氧预处理对所研究的任何脑区中EAAT1和ERβ的水平均无影响。EAAT2和ERα水平的相似变化模式表明，ERα可能在产生预处理作用时与EAAT2相互作用。缺氧预处理调节的内源性分子机制可能有助于缺氧诱导的缺血耐受性的形成，并可能为脑缺血治疗提供新的治疗靶点。
