BBA - General Subjects (v.1810, #1)

Redox atlas of the mouse by José Rodrigo Godoy; Maria Funke; Waltraud Ackermann; Petra Haunhorst; Sabrina Oesteritz; Francisco Capani; Hans-Peter Elsässer; Christopher Horst Lillig (2-92).
Oxidoreductases of the thioredoxin family of proteins have been thoroughly studied in numerous cellular and animal models mimicking human diseases. Despite of their well documented role in various disease conditions, no systematic information on the presence of these proteins is available.Here, we have systematically analyzed the presence of some of the major constituents of the glutaredoxin (Grx)-, peroxiredoxin (Prx)-, and thioredoxin (Trx)-systems, i.e. Grx1, Grx2, Grx3 (TXNL-2/PICOT), Grx5, nucleoredoxin (Nrx), Prx1, Prx2, Prx3, Prx4, Prx5, Prx6, Trx1, thioredoxin reductase 1 (TrxR1), Trx2, TrxR2, and γ-glutamyl cysteine synthetase (γ-GCS) in various tissues of the mouse using immunohistochemistry.The identification of the Trx family proteins in the central nervous system, sensory organs, digestive system, lymphatic system, reproductive system, urinary system, respiratory system, endocrine system, skin, heart, and muscle revealed a number of significant differences between these proteins with respect to their distribution in these tissues.Our results imply more specific functions and interactions between the proteins of this family than previously assumed.Crucial functions of Trx family proteins have been demonstrated in various disease conditions. A detailed overview on their distribution in various tissues will be helpful to fully comprehend their potential role and the interactions of these proteins in the most thoroughly studied model for human diseases—the laboratory mouse.This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases.
Keywords: Glutathione; Glutaredoxin; Peroxiredoxin; Thioredoxin; Thioredoxin reductase; Immunohistochemistry; Tissue distribution;

Thioredoxin and glutaredoxin system proteins—immunolocalization in the rat central nervous system by Maria Laura Aon-Bertolino; Juan Ignacio Romero; Pablo Galeano; Mariana Holubiec; Maria Sol Badorrey; Gustavo Ezequiel Saraceno; Eva-Maria Hanschmann; Christopher Horst Lillig; Francisco Capani (93-110).
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.
Keywords: Glutaredoxin; Glutathione; Peroxiredoxin; Thioredoxin; CNS; Brain;

Human Protein Atlas of redox systems — What can be learnt? by Pascal Dammeyer; Elias S.J. Arnér (111-138).
The freely available on-line data of immunohistochemical analyses for selected human redox proteins within the Human Protein Atlas were here analyzed, provided that reasonably solid data existed for the antibodies that were employed. This included tissue expression data for thioredoxin 1 (Trx1), Trx2, thioredoxin reductase 1 (TrxR1), TrxR2, glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PD), γ-glutamyl cysteinyl synthase (gGCS) and the six peroxiredoxins Prx1 to Prx6. The data were further complemented with a screen using a polyclonal peptide antibody raised against the unique glutaredoxin domain of TXNRD1_v3 (“v3”). The results from fifteen major tissues and organs are presented (lung, kidney, liver, lymph node, testis, prostate, ovary, breast, pancreas, cerebellum, hippocampus, cerebral cortex, skin, skeletal muscle and heart muscle) and discussed considering earlier findings described in the literature.Staining patterns proved to be highly variable and often unexpected both in terms of tissues analyzed and the individual target proteins. Among the analyzed tissues, only macrophages of the lung, tubular cells of the kidney, lymphoid cells of lymph nodes, Leydig cells in the testis, glandular cells of the prostate and exocrine glandular cells of the pancreas, showed positive staining with all of the fourteen antibodies that were analyzed. Among these antibodies, those against Trx1, TrxR2 and G6PD showed the most restricted staining across different tissues, while others including the antibodies against Trx2, TrxR1, GR, Prx3, Prx4 and Prx6 gave strong staining in most tissues. Staining for v3 was strong in many cells and tissues, which was unexpected considering previous results mapping transcripts for this protein. No obvious co-variation in staining across tissues could be noted when comparing any two of the analyzed antibodies. Staining for G6PD was weak in most tissues, except for cells of the seminiferous ducts in testis and follicular cells of the ovary, where G6PD staining was strong.Results from high-throughput screening projects such as the Human Protein Atlas must be taken with caution and need to be duly confirmed by thorough in-depth follow-up studies. The varying staining intensities comparing tissues as seen here for most of the analyzed antibodies nonetheless suggest that the overall profile of the human redox systems may vary significantly between different cell types and between different tissues.The Human Protein Atlas data suggest that the individual proteins of the human thioredoxin and glutathione systems may be strikingly tissue- and cell type-specific in terms of expression levels, but we also conclude that these type of high-throughput results should be taken with significant caution and must be duly verified using subsequent focused and detailed hypothesis-guided follow-up studies.This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases.
Keywords: Redox; Immunohistochemistry; Human; Thioredoxin; Glutathione; Peroxiredoxin;