Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat
Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat
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DOI：
10.1021/pr060209x
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Perez-Polo, J. Regino
中科院分区：
文献类型：
--
作者：
Hu, Xiaoming;Rea, Harriett C.;Perez-Polo, J. Regino
围产期缺氧/缺血（HI）是儿童神经功能缺损的常见原因。我们的目标是阐明导致 HI 诱发脑损伤的神经后遗症的潜在机制。通过永久性结扎雌性 P7 大鼠的左颈动脉，然后进行 90 分钟的缺氧（7.8% O-2）来诱导 HI。二维差异蛋白质组分析用于评估 HI 后 2 小时皮质中蛋白质表达的变化。通过质谱分析，总共鉴定出 17 种蛋白质，与假处理组相比，HI 后的表达扰动是假处理组的 2 倍或更高。在改变的蛋白质中，14-3-3 epsilon 和 TUC-2 在中枢神经系统的发育中发挥着重要作用，在 HI 后减少，这与皮质发育的早期紊乱一致。 DARPP-32 和 α-突触核蛋白（两种对多巴胺神经传递很重要的蛋白质）也受到影响，在 HI 损伤后 2 小时内增加了 2 倍以上。这些蛋白质的差异表达通过单独的蛋白质印迹测定进行了验证。 HI 脑损伤后早期，几种代谢酶和翻译因子的表达也受到干扰。这些发现为HI后神经退行性事件的机制提供了初步见解，并可能有助于合理设计增强HI后神经元适应和补偿的治疗策略。
Perinatal hypoxia/ ischemia ( HI) is a common cause of neurological deficits in children. Our goal was to elucidate the underlying mechanisms that contribute to the neurological sequelae of HI-induced brain injury. HI was induced by permanent ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O-2) in female P7 rats. A two-dimensional differential proteome analysis was used to assess changes in protein expression in cortex 2 h after HI. In total, 17 proteins reflecting a 2-fold or higher perturbation of expression after HI as compared to sham-treated pups were identified by mass spectrometry. Of the altered proteins, 14-3-3 epsilon and TUC-2, both playing an important role in the development of the central nervous system, decrease after HI, consistent with an early disturbance of cortical development. Also affected, DARPP-32 and alpha-synuclein, two proteins important for dopamine neurotransmission, increased more than 2-fold 2 h after HI injury. The differential expression of these proteins was validated by individual Western blot assays. The expression of several metabolic enzymes and translational factors was also perturbed early after HI brain injury. These findings provide initial insights into the mechanisms underlying neurodegenerative events after HI and may allow for the rational design of therapeutic strategies that enhance neuronal adaptation and compensation after HI.