Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain
Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain
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硫氧还蛋白缺乏会增加氧化应激并导致大鼠中脑双侧对称变性
DOI：
10.1016/j.nbd.2022.105921
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发表时间：
2022
影响因子：
6.1
通讯作者：
Mashimo T.
中科院分区：
文献类型：
--
作者：
Ohmori I;Ouchida M;Imai H;Ishida S;Toyokuni S;Mashimo T.
硫氧还蛋白（Thioredoxin，Txn 1）是一种重要的抗氧化剂，通过调节相互作用蛋白质的二巯基/二硫键平衡来对抗氧化应激。硫氧还蛋白在中枢神经系统（CNS）中的作用在很大程度上是未知的。一项针对N-乙基-N-亚硝基脲突变大鼠的表型驱动研究揭示了Txn 1突变在中枢神经系统退化中的重要性。在癫痫大鼠中进行了Txn 1-F54 L基因定位。Txn 1-F54 L的胰岛素降低活性约为野生型（WT）的三分之一。Txn 1-F54 L组大鼠中脑主要是丘脑和下丘出现对称性空泡变性。病变显示神经元和少突胶质细胞死亡。Txn 1-F54 L大鼠神经元线粒体出现形态学改变。核仁变性在5周龄时达到高峰，并在7周龄时开始自发修复。TUNEL检测表明，来源于纯合子的成纤维细胞在氧化应激下易受细胞死亡的影响。在5周龄WT大鼠中，丘脑的能量代谢显著高于大脑皮质。总之，在幼年大鼠中，Txn 1似乎在降低具有高能量代谢的中脑中的氧化应激中发挥重要作用。
Thioredoxin, encoded byTxn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of thioredoxin in the central nervous system (CNS) is largely unknown. A phenotype-driven study ofN-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed the importance ofTxn1mutations in CNS degeneration. Genetic mapping identifiedTxn1-F54L in the epileptic rats. The insulin-reducing activity ofTxn1-F54L was approximately one-third of that of the wild-type (WT). Bilateral symmetrical vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in theTxn1-F54L rats. The lesions displayed neuronal and oligodendrocytic cell death. Neurons inTxn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration peaked at five weeks of age, and spontaneous repair began at seven weeks. The TUNEL assay showed that fibroblasts derived from homozygotes were susceptible to cell death under oxidative stress. In five-week-old WT rats, energy metabolism in the thalamus was significantly higher than that in the cerebral cortex. In conclusion, in juvenile rats,Txn1seems to play an essential role in reducing oxidative stress in the midbrains with high energy metabolism.
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DOI：
10.1073/pnas.87.21.8282
发表时间：
1990-11
影响因子：
11.1
作者：
Naomi Wakasugi;Yutaka TAGAYAt;Hiro Wakasugi;Akira Mitsui;Michiyuki Maeda;Junji YODOIt;Thomas Tursz-Thom
通讯作者：
Naomi Wakasugi;Yutaka TAGAYAt;Hiro Wakasugi;Akira Mitsui;Michiyuki Maeda;Junji YODOIt;Thomas Tursz-Thom
影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
29.7
作者：
Nayak D;Roth TL;McGavern DB
通讯作者：
McGavern DB
影响因子：
11.2
作者：
Amanda F. Baker;Claire M. Payne;M. Briehl;Garth Powis
通讯作者：
Amanda F. Baker;Claire M. Payne;M. Briehl;Garth Powis
DOI：
10.1172/jci17700
发表时间：
2003-11
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Mitsutaka Yamamoto;Guiping Yang;C. Hong;Jing Liu;E. Holle;Xianzhong Yu;T. Wagner;S. Vatner;
通讯作者：
Mitsutaka Yamamoto;Guiping Yang;C. Hong;Jing Liu;E. Holle;Xianzhong Yu;T. Wagner;S. Vatner;