Acute hypoxia modifies regulation of neuroglobin in the neonatal mouse brain
Acute hypoxia modifies regulation of neuroglobin in the neonatal mouse brain
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DOI：
10.1016/j.expneurol.2012.04.006
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发表时间：
2012-07-01
影响因子：
5.3
通讯作者：
Trollmann, Regina
中科院分区：
文献类型：
--
作者：
Huemmler, Nicolas;Schneider, Christina;Trollmann, Regina
在内源性低氧适应系统中，脑红蛋白被认为是一种新的氧依赖神经保护剂。我们的目的是研究：(1)常氧和低氧条件下发育的小鼠脑内脑红蛋白的成熟年龄相关调节；(2)低氧诱导转录因子(HIF)在体外和体内作为氧依赖的脑红蛋白调节的可能媒介的作用。通过免疫组织化学分析，我们证实在常氧条件下，脑红蛋白表达在发育中的神经元的细胞质中，而不是胶质细胞中。未成熟脑(P0，P7)暴露于急性(8%O-2，6h)和慢性全身性低氧(10%O-2，7d)中，脑红蛋白的激活随成熟阶段(P0，P7)和缺氧程度的不同而不同。这一观察结果可能表明脑红蛋白参与了小鼠脑成熟早期未成熟神经元对急性缺氧的适应性反应(P0)。在正常氧和低氧(1%O-2)条件下，原代培养的小鼠皮质神经元(DIV6)经Pro-4-羟基酶抑制剂(FG-4497)激活后，脑红蛋白基因表达显著上调。综上所述，目前的结果有力地表明，大脑对脑红蛋白的调节与成熟阶段有关，低氧诱导的脑红蛋白上调被HIF系统改变。(C)2012 Elsevier Inc.保留所有权利。
Among endogenous adaptive systems to hypoxia, neuroglobin, a recently discovered heme protein, was suggested as a novel oxygen-dependent neuroprotectant We aimed to characterize i) maturational age-related regulation of neuroglobin in the developing mouse brain under normoxic and hypoxic conditions, and ii) the role of hypoxia-inducible transcription factors (HIFs) as possible mediators of O-2-dependent regulation of neuroglobin in vitro and in vivo.During early stages of postnatal brain maturation (P0-P14) neuroglobin mRNA levels significantly increased in developing mouse forebrains. By immunohistochemical analysis we confirmed expression of neuroglobin protein in the cytoplasm of developing neurons but not glial cells under normoxic conditions. Exposure of the immature brains (P0, P7) to acute (8% O-2, 6 h) and chronic systemic hypoxia (10% O-2, 7 days) led to differential activation of neuroglobin varying with maturational stage (P0, P7) and severity of hypoxia. This observation may indicate that neuroglobin is involved in adaptive responses of immature neurons to acute hypoxia during an early stage of mouse brain maturation (P0). In response to activation of the HIF system by prolyl-4-hydroxylase inhibitor (FG-4497), neuroglobin mRNA expression was significantly up-regulated in primary mouse cortical neurons (DIV6) exposed to normoxia and hypoxia (1% O-2) compared to non-treated controls. In conclusion, present results strongly indicate that cerebral regulation of neuroglobin is related to maturational stage and that hypoxia-induced neuroglobin up-regulation is modified by the HIF system. (C) 2012 Elsevier Inc. All rights reserved.