Thioredoxin and glutaredoxin system proteins-immunolocalization in the rat central nervous system

Abstract

Background: The oxidoreductases of the thioredoxin (Trx) family of proteins play a major role in the cellularresponse to oxidative stress. Redox imbalance is a major feature of brain damage. For instance, neuronaldamage and glial reaction induced by a hypoxic–ischemic episode is highly related to glutamateexcitotoxicity, oxidative stress and mitochondrial dysfunction. Most animal models of hypoxia–ischemiain 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.Methods: The aim of this work was to study the distribution of the following proteins of the thioredoxin andglutathione/glutaredoxin (Grx) systems in the rat CNS by immunohistochemistry: Trx1, Trx2, TrxR1, TrxR2,Txnip, Grx1, Grx2, Grx3, Grx5, and ã-GCS, peroxiredoxin 1 (Prx1), Prx2, Prx3, Prx4, Prx5, and Prx6. We havefocused on areas most sensitive to a hypoxia–ischemic insult: Cerebellum, striatum, hippocampus, spinalcord, substantia nigra, cortex and retina.Results and conclusions: Previous studies implied that these redox proteins may be distributed in most celltypes 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.General significance: 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 disorder of the CNS. This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases.