Aon-Bertolino Maria Laura, Romero Juan Ignacio, Galeano Pablo, Holubiec Mariana, Badorrey Maria Sol, Saraceno Gustavo Ezequiel, Hanschmann Eva-Maria, Lillig Christopher Horst, Capani Francisco
Universidad de Buenos Aires Facultad de Medicina and Comisión Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Biochim Biophys Acta. 2011 Jan;1810(1):93-110. doi: 10.1016/j.bbagen.2010.06.011. Epub 2010 Jul 8.
The oxidoreductases of the thioredoxin (Trx) family of proteins play a major role in the cellular response to oxidative stress. Redox imbalance is a major feature of brain damage. For instance, neuronal damage and glial reaction induced by a hypoxic-ischemic episode is highly related to glutamate excitotoxicity, oxidative stress and mitochondrial dysfunction. Most animal models of hypoxia-ischemia in the central nervous system (CNS) use rats to study the mechanisms involved in neuronal cell death, however, no comprehensive study on the localization of the redox proteins in the rat CNS was available.
The aim of this work was to study the distribution of the following proteins of the thioredoxin and glutathione/glutaredoxin (Grx) systems in the rat CNS by immunohistochemistry: Trx1, Trx2, TrxR1, TrxR2, Txnip, Grx1, Grx2, Grx3, Grx5, and γ-GCS, peroxiredoxin 1 (Prx1), Prx2, Prx3, Prx4, Prx5, and Prx6. We have focused on areas most sensitive to a hypoxia-ischemic insult: Cerebellum, striatum, hippocampus, spinal cord, substantia nigra, cortex and retina.
Previous studies implied that these redox proteins may be distributed in most cell types and regions of the CNS. Here, we have observed several remarkable differences in both abundance and regional distribution that point to a complex interplay and crosstalk between the proteins of this family.
We think that these data might be helpful to reveal new insights into the role of thiol redox pathways in the pathogenesis of hypoxia-ischemia insults and other disorders of the CNS. This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases.
硫氧还蛋白（Trx）家族的氧化还原酶在细胞对氧化应激的反应中起主要作用。氧化还原失衡是脑损伤的一个主要特征。例如，缺氧缺血发作诱导的神经元损伤和神经胶质反应与谷氨酸兴奋性毒性、氧化应激和线粒体功能障碍高度相关。中枢神经系统（CNS）中大多数缺氧缺血动物模型使用大鼠来研究神经元细胞死亡所涉及的机制，然而，尚无关于大鼠中枢神经系统中氧化还原蛋白定位的全面研究。
本研究的目的是通过免疫组织化学研究硫氧还蛋白和谷胱甘肽/谷氧还蛋白（Grx）系统的以下蛋白质在大鼠中枢神经系统中的分布：Trx1、Trx2、TrxR1、TrxR2、Txnip、Grx1、Grx2、Grx3、Grx5和γ-GCS、过氧化物酶1（Prx1）、Prx2、Prx3、Prx4、Prx5和Prx6。我们重点关注对缺氧缺血损伤最敏感的区域：小脑、纹状体、海马、脊髓、黑质、皮质和视网膜。
先前的研究表明，这些氧化还原蛋白可能分布于中枢神经系统的大多数细胞类型和区域。在此，我们观察到在丰度和区域分布上的几个显著差异，这表明该家族蛋白质之间存在复杂的相互作用和串扰。
我们认为这些数据可能有助于揭示硫醇氧化还原途径在缺氧缺血性损伤和中枢神经系统其他疾病发病机制中的作用的新见解。本文是名为“人类和小鼠氧化还原蛋白图谱”的特刊的一部分。
