Mitochondrial peroxiredoxin-3 protects hippocampal neurons from excitotoxic injury in vivo
Mitochondrial peroxiredoxin-3 protects hippocampal neurons from excitotoxic injury in vivo
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DOI：
10.1046/j.1471-4159.2003.01918.x
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发表时间：
2003-08-01
影响因子：
4.7
通讯作者：
Oikawa, S
中科院分区：
文献类型：
--
作者：
Hattori, F;Murayama, N;Oikawa, S
线粒体参与神经细胞的兴奋性毒性损伤。在线粒体的钙缓冲能力被破坏后，线粒体钙超载诱导活性氧（ROS）爆发，其产生自由基并打开渗透性转换孔，最终导致神经元细胞死亡。在本研究中，我们专注于线粒体抗氧化蛋白，过氧化物酶-3（Prx-3），研究损伤神经细胞线粒体中ROS毒性上调的机制。免疫组织化学分析显示，Prx-3蛋白存在于大鼠海马线粒体，而我们发现，Prx-3的mRNA和蛋白水平的显着下降与硝基蛋白在大鼠海马损伤鹅膏蕈氨酸的显微注射。此外，在体内的腺病毒基因转移的Prx-3完全抑制蛋白质硝化和显着减少神经胶质增生，神经元细胞死亡后的事件。由于线粒体Prx-3似乎对氧化损伤具有神经保护作用，我们的研究结果表明，Prx-3上调可能是一种有用的新方法，用于管理神经退行性疾病。
Mitochondria are involved in excitotoxic damage of nerve cells. Following the breakdown of the calcium-buffering ability of mitochondria, mitochondrial calcium overload induces reactive oxygen species (ROS) bursts that produce free radicals and open permeability transition pores, ultimately leading to neuronal cell death. In the present study, we focused on a mitochondrial antioxidant protein, peroxiredoxin-3 (Prx-3), to investigate the mechanism by which toxic properties of ROS were up-regulated in mitochondria of damaged nerve cells. Immunohistochemical analysis revealed that Prx-3 protein exists in mitochondria of rat hippocampus, whereas we found a significant decrease in Prx-3 mRNA and protein levels associated with an increase in nitrated proteins in the rat hippocampus injured by microinjection of ibotenic acid. Furthermore, in vivo adenoviral gene transfer of Prx-3 completely inhibited protein nitration and markedly reduced gliosis, a post-neuronal cell death event. Since mitochondrial Prx-3 seems to be neuroprotective against oxidative insults, our findings suggest that Prx-3 up-regulation might be a useful novel approach for the management of neurodegenerative diseases.