Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3β survival signaling
Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3β survival signaling
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DOI：
10.1038/sj.jcbfm.9600399
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发表时间：
2007-05-01
影响因子：
6.3
通讯作者：
Chan, Pak H.
中科院分区：
文献类型：
--
作者：
Endo, Hidenori;Nito, Chikako;Chan, Pak H.
最近的研究表明，氧化应激在几种神经退行性疾病模型中具有有害作用，包括蛛网膜下腔出血（SAH）。然而，氧化应激如何影响SAH后的急性脑损伤仍不清楚。我们以前曾报道过，铜/锌超氧化物歧化酶（SOD 1）的过度表达减少脑缺血后的氧化应激和随后的神经元损伤。在这项研究中，我们调查了氧化应激和急性脑损伤后SAH使用SOD 1转基因（Tg）大鼠。SAH是通过野生型（Wt）和SOD 1 Tg大鼠的血管内穿孔产生的。与Wt大鼠相比，通过细胞死亡测定检测到的24小时的凋亡细胞死亡在SOD 1 Tg大鼠的大脑皮层中显著降低。SOD 1 Tg大鼠24 h死亡率也显著降低。一项氢乙啶研究表明，超氧阴离子的产生SAH后，减少在SOD 1 Tg大鼠的大脑皮层。此外，Akt和糖原合成酶激酶-3 β（GSK 3 β）的磷酸化，这是在凋亡细胞死亡的生存信号，在SAH后的SOD 1 Tg大鼠的大脑皮层中，使用蛋白质印迹分析和免疫组织化学更增强。我们的结论是，SOD 1过表达减少氧化应激可能通过激活Akt/GSK 3 β生存信号来减轻SAH后的急性脑损伤。
Recent studies have revealed that oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). However, how oxidative stress affects acute brain injury after SAH remains unknown. We have previously reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduces oxidative stress and subsequent neuronal injury after cerebral ischemia. In this study, we investigated the relationship between oxidative stress and acute brain injury after SAH using SOD1 transgenic ( Tg) rats. SAH was produced by endovascular perforation in wild- type (Wt) and SOD1 Tg rats. Apoptotic cell death at 24 h, detected by a cell death assay, was significantly decreased in the cerebral cortex of the SOD1 Tg rats compared with the Wt rats. The mortality rate at 24 h was also significantly decreased in the SOD1 Tg rats. A hydroethidine study demonstrated that superoxide anion production after SAH was reduced in the cerebral cortex of the SOD1 Tg rats. Moreover, phosphorylation of Akt and glycogen synthase kinase-3 beta (GSK3 beta), which are survival signals in apoptotic cell death, was more enhanced in the cerebral cortex of the SOD1 Tg rats after SAH using Western blot analysis and immunohistochemistry. We conclude that reduction in oxidative stress by SOD1 overexpression may attenuate acute brain injury after SAH via activation of Akt/GSK3 beta survival signaling.