Takagi Y, Mitsui A, Nishiyama A, Nozaki K, Sono H, Gon Y, Hashimoto N, Yodoi J
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507 Japan.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4131-6. doi: 10.1073/pnas.96.7.4131.
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 wild-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 1 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.
硫氧还蛋白（TRX）在细胞内和细胞外区室均发挥重要生物学作用，包括通过硫醇氧化还原控制调节各种细胞内分子。我们培育了过表达TRX的小鼠，并证实野生型（WT）小鼠和TRX转基因（Tg）小鼠在解剖学和生理学上没有差异。在本研究中，我们对小鼠进行局灶性脑缺血，以阐明TRX在脑缺血损伤中的作用。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有所改善。细胞蛋白氧化标志物蛋白羰基含量在缺血损伤后，Tg小鼠的增加幅度小于WT小鼠。此外，缺血1小时后，Tg小鼠中的c-fos表达强于WT小鼠。我们的结果表明，TRX的转基因表达减少了缺血性神经元损伤，并且TRX以及由TRX修饰的氧化还原状态在中风期间的脑损伤中起关键作用。
