scholarly journals Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase

Cell Reports ◽  
2017 ◽  
Vol 19 (13) ◽  
pp. 2771-2781 ◽  
Author(s):  
Justin R. Prigge ◽  
Lucia Coppo ◽  
Sebastin S. Martin ◽  
Fernando Ogata ◽  
Colin G. Miller ◽  
...  
Keyword(s):  
Glutathione Reductase ◽  
Thioredoxin Reductase ◽  
Thioredoxin Reductase 1 ◽  
Thioredoxin 1

scholarly journals Interplay between cytosolic disulfide reductase systems and the Nrf2/Keap1 pathway

2015 ◽  
Vol 43 (4) ◽  
pp. 632-638 ◽  
Author(s):  
Edward E. Schmidt
Keyword(s):  
Oxidative Stress ◽  
Thioredoxin Reductase ◽  
Reducing Power ◽  
Nuclear Factor ◽  
Independent Source ◽  
Nrf2 Pathway ◽  
Thioredoxin Reductase 1 ◽  
Disulfide Reductase ◽  
The Status ◽  
Thioredoxin 1

NADPH transfers reducing power from bioenergetic pathways to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR) to support essential reductive systems. Surprisingly, it was recently shown that mouse livers lacking both TrxR1 and GR (‘TR/GR-null’) can sustain redox (reduction-oxidation) homoeostasis using a previously unrecognized NADPH-independent source of reducing power fuelled by dietary methionine. The NADPH-dependent systems are robustly redundant in liver, such that disruption of either TrxR1 or GR alone does not cause oxidative stress. However, disruption of TrxR1 induces transcription factor Nrf2 (nuclear factor erythroid-derived 2-like-2) whereas disruption of GR does not. This suggests the Nrf2 pathway responds directly to the status of the thioredoxin-1 (Trx1) system. The proximal regulator of Nrf2 is Keap1 (Kelch-like ECH-associated protein-1), a cysteine (Cys)-rich protein that normally interacts transiently with Nrf2, targeting it for degradation. During oxidative stress, this interaction is stabilized, preventing degradation of newly synthesized Nrf2, thereby allowing Nrf2 accumulation. Within the Trx1 system, TrxR1 and peroxiredoxins (Prxs) contain some of the most reactive nucleophilic residues in the cell, making them likely targets for oxidants or electrophiles. We propose that Keap1 activity and therefore Nrf2 is regulated by interactions of Trx1 system enzymes with oxidants. In TR/GR-null livers, Nrf2 activity is further induced, revealing that TrxR-independent systems also repress Nrf2 and these might be induced by more extreme challenges.

scholarly journals Thioredoxin reductase-1 knock down does not result in thioredoxin-1 oxidation

2008 ◽  
Vol 368 (3) ◽  
pp. 832-836 ◽  
Author(s):  
Walter H. Watson ◽  
Jacqueline M. Heilman ◽  
Laura L. Hughes ◽  
Jeanine C. Spielberger
Keyword(s):  
Thioredoxin Reductase ◽  
Knock Down ◽  
Thioredoxin Reductase 1 ◽  
Thioredoxin 1

Effect of mercury(II) on Nrf2, thioredoxin reductase-1 and thioredoxin-1 in human monocytes

2008 ◽  
Vol 24 (6) ◽  
pp. 765-772 ◽  
Author(s):  
John C. Wataha ◽  
Jill B. Lewis ◽  
Veronica V. McCloud ◽  
Melissa Shaw ◽  
Yo Omata ◽  
...  
Keyword(s):  
Thioredoxin Reductase ◽  
Human Monocytes ◽  
Thioredoxin Reductase 1 ◽  
Thioredoxin 1

Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activity

FEBS Letters ◽  
2006 ◽  
Vol 580 (15) ◽  
pp. 3595-3600 ◽  
Author(s):  
Sabine Urig ◽  
Johanna Lieske ◽  
Karin Fritz-Wolf ◽  
Angelika Irmler ◽  
Katja Becker
Keyword(s):  
Glutathione Reductase ◽  
Reductase Activity ◽  
Thioredoxin Reductase ◽  
Thioredoxin Reductase 1 ◽  
Glutathione Reductase Activity

scholarly journals The Cellular Thioredoxin-1/Thioredoxin Reductase-1 Driven Oxidoreduction Represents a Chemotherapeutic Target for HIV-1 Entry Inhibition

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147773 ◽  
Author(s):  
Kathrin Reiser ◽  
Leen Mathys ◽  
Sophie Curbo ◽  
Christophe Pannecouque ◽  
Sam Noppen ◽  
...  
Keyword(s):  
Thioredoxin Reductase ◽  
Thioredoxin Reductase 1 ◽  
Thioredoxin 1 ◽  
Hiv 1 ◽  
Entry Inhibition

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

scholarly journals Oxidative stress response in regulatory and conventional T cells: a comparison between patients with chronic coronary syndrome and healthy subjects

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Anna K. Lundberg ◽  
Rosanna W. S. Chung ◽  
Louise Zeijlon ◽  
Gustav Fernström ◽  
Lena Jonasson
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Thioredoxin Reductase ◽  
Healthy Controls ◽  
Antioxidant Genes ◽  
Consistent Finding ◽  
Coronary Syndrome ◽  
Thioredoxin Reductase 1

Abstract Background Inflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+ T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Treg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In this pilot study, we tested the hypothesis that oxidative stress might be a potential contributor to the Treg cell deficit in CCS patients. Methods Thirty patients with CCS and 24 healthy controls were included. Treg (CD4+CD25+CD127−) and conventional T (CD4+CD25−, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Treg and Tconv cells. Also, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells, and oxidized (ox) LDL/LDL ratios were determined in plasma. Results At all doses of H2O2, Treg cells accumulated more ROS and exhibited higher rates of death than their Tconv counterparts, p < 0.0001. Treg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001, while oxLDL/LDL ratios were higher, 29 vs 22, p = 0.006. Conclusion Treg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress may play a role in the reduction of Treg cells in vivo.

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