Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha
Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha
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DOI：
10.1016/j.neulet.2005.05.006
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发表时间：
2005-09-02
影响因子：
2.5
通讯作者：
Beart, PM
中科院分区：
文献类型：
--
作者：
Cimarosti, H;Jones, NM;Beart, PM
将大脑暴露于亚致死性损伤可以防止随后的脑损伤。缺氧预处理诱导新生大鼠脑缺氧缺血耐受及其与基因和蛋白表达的关系为研究兴奋性氨基酸转运体（EAAT 1和EAAT 2）和雌激素受体（ER α和ER β）在新生大鼠缺氧诱导的缺血耐受中的作用，我们检测了亚致死性缺氧（8%02，3h）后不同时间点新生大鼠皮层、海马和纹状体中这些蛋白表达的变化。通过形态学评估确定，与同窝对照动物相比，缺氧缺血前24 h缺氧预处理提供了显著的脑保护。免疫印迹分析显示，EAAT 2和ER α在缺氧预处理后24 h在皮质中分别显著增加55%和49%。令人惊讶的是，在同一时间点，观察到纹状体中EAAT 2显著降低48%。相比之下，低氧预处理对在任何分析的时间点研究的任何脑区域中的EAAT 1和ER β水平没有影响。EAAT 2和ER α水平变化的相似模式表明，ER α可能与EAAT 2在产生预适应中相互作用。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的形成，并可能为脑缺血的治疗提供新的治疗靶点。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
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 (ER alpha and ER beta) 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% 02, 3 h). Preconditioning with hypoxia 24 h before hypoxia-ischemia afforded marked brain protection compared with littermate control animals as determined by morphological assessment. Immunoblot analysis showed that EAAT2 and ER alpha were significantly increased by 55% and 49%, respectively, in cortex at 24 h 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 ER beta in any of the brain regions studied at any of the time points analyzed. The similar pattern of changes in EAAT2 and ER alpha levels suggests that ER alpha 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.