Proteomic analysis of CA1 and CA3 regions of rat hippocampus and differential susceptibility to intermittent hypoxia
Proteomic analysis of CA1 and CA3 regions of rat hippocampus and differential susceptibility to intermittent hypoxia
复制标题
DOI：
10.1046/j.1471-4159.2002.01134.x
复制
发表时间：
2002-10-01
影响因子：
4.7
通讯作者：
Klein, JB
中科院分区：
文献类型：
--
作者：
Gozal, E;Gozal, D;Klein, JB
海马体的CA1和CA3区域在它们对缺氧的易感性方面通常显著不同，并且更特别地对以睡眠呼吸暂停为特征的间歇性缺氧。蛋白质组学方法被用来确定差异表达的蛋白质在CA1和CA3区的大鼠海马和评估蛋白质表达的变化后，6小时暴露于间歇性缺氧（IH）。共鉴定出99种蛋白质，其中15种在CA1和CA3区域差异表达。IH后，CA1区有32个蛋白质表达上调，CA3区仅有7个蛋白质表达上调。CA1区缺氧调节蛋白包括结构蛋白、凋亡相关蛋白、主要是分子伴侣蛋白和参与细胞代谢途径的蛋白。我们的结论是IH介导的CA1损伤的结果，从复杂的相互作用的途径，包括增加代谢，诱导应激诱导蛋白和凋亡，并最终破坏结构蛋白和细胞的完整性。这些研究结果提供了初步的见解，在神经组织缺氧的易感性差异的机制，并可能允许未来描绘的干预策略，旨在提高神经适应IH。
The CA1 and CA3 regions of the hippocampus markedly differ in their susceptibility to hypoxia in general, and more particularly to the intermittent hypoxia that characterizes sleep apnea. Proteomic approaches were used to identify proteins differentially expressed in the CA1 and CA3 regions of the rat hippocampus and to assess changes in protein expression following a 6-h exposure to intermittent hypoxia (IH). Ninety-nine proteins were identified, and 15 were differentially expressed in the CA1 and the CA3 regions. Following IH, 32 proteins in the CA1 region and only 7 proteins in the more resistant CA3 area were up-regulated. Hypoxia-regulated proteins in the CA1 region included structural proteins, proteins related to apoptosis, primarily chaperone proteins, and proteins involved in cellular metabolic pathways. We conclude that IH-mediated CA1 injury results from complex interactions between pathways involving increased metabolism, induction of stress-induced proteins and apoptosis, and, ultimately, disruption of structural proteins and cell integrity. These findings provide initial insights into mechanisms underlying differences in susceptibility to hypoxia in neural tissue, and may allow for future delineation of interventional strategies aiming to enhance neuronal adaptation to IH.