Thioredoxin Reductase 1 Modulates Pigmentation and Photobiology of Murine Melanocytes in vivo

Background. Aurothioglucose- (ATG-) mediated inhibition of thioredoxin reductase-1 (TXNRD1) improves alveolarization in experimental murine bronchopulmonary dysplasia (BPD). Glutathione (GSH) mediates susceptibility to neonatal and adult oxidative lung injury. We have previously shown that ATG attenuates hyperoxic lung injury and enhances glutathione- (GSH-) dependent antioxidant defenses in adult mice. Hypothesis. The present studies evaluated the effects of TXNRD1 inhibition on GSH-dependent antioxidant defenses in newborn mice in vivo and lung epithelia in vitro. Methods. Newborn mice received intraperitoneal ATG or saline prior to room air or 85% hyperoxia exposure. Glutamate-cysteine ligase (GCL) catalytic (Gclc) and modifier (Gclm) mRNA levels, total GSH levels, total GSH peroxidase (GPx) activity, and Gpx2 expression were determined in lung homogenates. In vitro, murine transformed club cells (mtCCs) were treated with the TXNRD1 inhibitor auranofin (AFN) or vehicle in the presence or absence of the GCL inhibitor buthionine sulfoximine (BSO). Results. In vivo, ATG enhanced hyperoxia-induced increases in Gclc mRNA levels, total GSH contents, and GPx activity. In vitro, AFN increased Gclm mRNA levels, intracellular and extracellular GSH levels, and GPx activity. BSO prevented AFN-induced increases in GSH levels. Conclusions. Our data are consistent with a model in which TXNRD1 inhibition augments hyperoxia-induced GSH-dependent antioxidant responses in neonatal mice. Discrepancies between in vivo and in vitro results highlight the need for methodologies that permit accurate assessments of the GSH system at the single-cell level.

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Thioredoxin Reductase 1 Expression in Colon Cancer: Discrepancy between In Vitro and In Vivo Findings

Laboratory Investigation ◽

10.1097/01.lab.0000085189.47968.f8 ◽

2003 ◽

Vol 83 (9) ◽

pp. 1321-1331 ◽

Cited By ~ 14

Author(s):

Sandra Lechner ◽

Ulf Müller-Ladner ◽

Elena Neumann ◽

Tanja Spöttl ◽

Klaus Schlottmann ◽

...

Keyword(s):

Colon Cancer ◽

Thioredoxin Reductase ◽

Thioredoxin Reductase 1

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Selenide Chitosan Sulfate Improved The Hepatocyte Activity, Growth Performance, and Anti-Oxidation Ability by Activating The Thioredoxin Reductase of Chickens In Vitro and In Vivo

10.21203/rs.3.rs-76175/v1 ◽

2020 ◽

Author(s):

Lele Hou ◽

Huiling Qiu ◽

Lianqin Zhu ◽

Yufeng Huang ◽

Shansong Gao ◽

...

Keyword(s):

Growth Performance ◽

Culture Medium ◽

Thioredoxin Reductase ◽

Dietary Supplementation ◽

Control Group ◽

Treatment Groups ◽

Thioredoxin Reductase 1 ◽

Specific Pathogen

Abstract Background: There are very few studies on the synergy effects of biological antioxidant activity on selenium (Se) and sulfate. This study evaluated the effect of selenide chitosan sulfate (LS-COS-Se) on the hepatocytes activity, growth performance, and anti-oxidation ability by activating the thioredoxin reductase (TrxR) system of specific pathogen free (SPF) chickens in vitro and in vivo. Methods: The hepatocytes were obtained in vitro and a total of 240 SPF White Leghorns chickens (7 days of age and body weight of 45.0 ± 2.0 g) were collected in vivo. The hepatocytes and chickens were randomly allocated into six treatment groups: control group; chitosan (COS) group; sodium selenite (Na2SeO3) group; selenide chitosan (COS-Se) group; chitosan sulfate (LS-COS) group; LS-COS-Se group. After 24 h, the culture medium and hepatocytes were collected and preserved respectively for analyzing the metabolic activity of hepatocytes. Gowth performance was evaluated and chickens were euthanized to obtain plasma and liver tissue to measure antioxidant associated parameter on days 14 and 28. Results: The experiment in vitro showed that the activities of TrxR, superoxide dismutase (SOD), catalase (CAT) in culture medium and the levels of thioredoxin reductase 1 (TrxR-1) and thioredoxin reductase 3 (TrxR-3) mRNA in hepatocytes in LS-COS-Se group were significantly higher (P < 0.05), but the content of malondialdehyde (MDA) and the activity of lactate dehydrogenase (LDH) significantly decreased (P < 0.05) than those in control, COS and LS-COS groups. Compared with Na2SeO3 and COS-Se groups, the levels of TrxR-1 and TrxR-3 mRNA in hepatocytes and the activity of SOD in culture medium significantly increased in LS-COS-Se group (P < 0.05). The experiment in vivo showed that the baby weight on 14d and 28d, the activities of TrxR, SOD and anti-superoxide anion radical (AntiO2-) in plasma and the levels of TrxR-1 and TrxR-3 mRNA in liver of dietary supplementation with LS-COS-Se were significantly higher than those in control, COS and LS-COS groups (P < 0.05). The activities of TrxR and SOD in plasma of dietary supplementation with LS-COS-Se were significantly higher than those of Na2SeO3 group and COS-Se group (P < 0.05). Conclusion: LS-COS-Se as potential antioxidant improved the hepatocytes activity, growth performance, and anti-oxidation ability by activating the TrxR system of SPF chickens in vitro and in vivo. The better biological activity of LS-COS-Se was mainly due to the synergistic effect of Se and sulfate on TrxR system.

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

Nature Communications ◽

10.1038/s41467-021-21540-6 ◽

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.

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

Journal of Translational Medicine ◽

10.1186/s12967-021-02906-2 ◽

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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