Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage
Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage
复制标题
DOI：
10.1073/pnas.96.7.4131
复制
发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Yodoi, J
中科院分区：
文献类型：
--
作者：
Takagi, Y;Mitsui, A;Yodoi, J
硫氧还蛋白（TRX）在细胞内和细胞外都发挥着重要的生物学作用，包括通过硫醇氧化还原控制调节各种细胞内分子。我们制作了TRX过表达小鼠，证实了温和型（WT）小鼠和TRX转基因（Tg）小鼠在解剖和生理上没有差异。本研究通过小鼠局灶性脑缺血来揭示TRX在脑缺血损伤中的作用。在大脑中动脉闭塞后24小时，Tg小鼠的梗死面积和体积明显小于WT小鼠。此外，与WT小鼠相比，Tg小鼠的神经功能缺损得到改善。蛋白羰基含量是细胞蛋白氧化的标志，在缺血损伤后，Tg小鼠比WT小鼠增加较少。此外，c-fos在缺血1小时后在Tg小鼠中的表达强于WT小鼠。我们的研究结果表明，TRX的转基因表达减少了缺血性神经元损伤，TRX和TRX修饰的氧化还原状态在卒中脑损伤中起着至关重要的作用。
Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between mild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice I hr after ischemia, Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.