The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions.

Mammalian cytosolic thioredoxin reductase (TrxR1) serves as an antioxidant protein by transferring electrons from NADPH to various substrates. The action of TrxR1 is achieved via reversible changes between NADPH-reduced and non-reduced forms, which involves C-terminal selenolthiol/selenenylsulfide exchanges. TrxR1 may be released into extracellular environment, where TrxR1 is present mainly in the non-reduced form with active-site disulfide and selenenylsulfide bonds.

Elevated serum 4HNE plus decreased serum thioredoxin: Unique feature and implications for acute exacerbation of chronic obstructive pulmonary disease.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a global problem with high mortality. Its pathogenesis is not fully understood. To reveal new serum feature of AECOPD and their potential implications, we have analyzed 180 serum samples, and found that in the serum of AECOPD patients, 4-hydroxy-2-nonenal (4HNE)-protein adducts are dynamically increased as partial pressure of oxygen (PaO2) drops, which is accompanied by progressively decreasing thioredoxin reductase (TrxR1) and thioredoxin (Trx1), as compared with those of healthy people.

New insights into serum/extracellular thioredoxin in regulating hepatic insulin receptor activation.

Background: Serum thioredoxin of type-2 diabetic patients is significantly higher than that of healthy people. Pathophysiological significance is unclear.

Methods: Effects of serum/extracellular thioredoxin on phosphorylation (activation) of hepatic insulin receptor (IR) were investigated by using methods in biochemistry, cell/molecular biology and mass spectrometry.

Role and mechanism of homocysteine in affecting hepatic protein-tyrosine phosphatase 1B.

Background: Elevated homocysteine is epidemiologically related to insulin resistance. Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling. However, the effect of homocysteine on PTP1B remains unclear.

A novel protein tyrosine phosphatase 1B inhibitor with therapeutic potential for insulin resistance.

Background And Purpose: Insulin-sensitizing drugs are currently limited, and identifying new candidates is a challenge. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling, and its inhibition is anticipated to improve insulin resistance. Here, the pharmacological properties of CX08005, a novel PTP1B inhibitor, were investigated.

Bacterial thioredoxin and thioredoxin reductase as mediators for epigallocatechin 3-gallate-induced antimicrobial action.

Epigallocatechin 3-gallate (EGCG) is the most abundant catechin in green tea and may combat bacteria with few side-effects. Its selectivity for different bacterial infections remains unclear, and hence the identification of the underlying mechanism is of practical importance. Both the thioredoxin (Trx) system and the glutathione/glutaredoxin (Grx) system support bacterial growth.

New insights into the posttranslational regulation of human cytosolic thioredoxin by S-palmitoylation.

High level of palmitate is associated with metabolic disorders. We recently showed that enhanced level of S-palmitoylated cytosolic thioredoxin (Trx1) in mouse liver was new characteristic feature of insulin resistance. However, our understanding of the effect of S-palmitoylation on Trx1 is limited, and the tissue specificity of Trx1 S-palmitoylation is unclear.

Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic thioredoxin reductase and thioredoxin.

Overnutrition can lead to oxidative stress, but its underlying mechanism remains unclear. In this study, we report that human liver-derived HepG2 cells utilize cytosolic thioredoxin reductase (TrxR1) and thioredoxin (hTrx1) to defend against the high glucose/palmitate-mediated increase in reactive oxygen species. However, enhanced TrxR1/hTrx1 palmitoylation occurs in parallel with a decrease in their activities under the conditions studied here.

High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance.

High-fat diet (HFD) can induce oxidative stress. Thioredoxin (Trx) and thioredoxin reductase (TrxR) are critical antioxidant proteins but how they are affected by HFD remains unclear. Using HFD-induced insulin-resistant mouse model, we show here that liver Trx and TrxR are significantly decreased, but, remarkably, the degree of their S-acylation is increased after consuming HFD.

A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant effects of ambroxol.

Long-term treatment with ambroxol (ABX), a bronchial expectorant, was found to prevent acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The underlying mechanism remains unclear. To address this, we have investigated the effect of ABX on critical antioxidant proteins thioredoxin (Trx) and thioredoxin reductase (TrxR) that are decreased in patients with AECOPD.

Finite element analysis of pedestrian lower limb fractures by direct force: the result of being run over or impact?

The elucidation and prediction of the biomechanics of lower limb fractures could serve as a useful tool in forensic practices. Finite element (FE) analysis could potentially help in the understanding of the fracture mechanisms of lower limb fractures frequently caused by car-pedestrian accidents. Our aim was (1) to develop and validate a FE model of the human lower limb, (2) to assess the biomechanics of specific injuries concerning run-over and impact loading conditions, and (3) to reconstruct one real car-pedestrian collision case using the model created in this study.

Blunt liver injury with intact ribs under impacts on the abdomen: a biomechanical investigation.

Abdominal trauma accounts for nearly 20% of all severe traffic injuries and can often result from intentional physical violence, from which blunt liver injury is regarded as the most common result and is associated with a high mortality rate. Liver injury may be caused by a direct impact with a certain velocity and energy on the abdomen, which may result in a lacerated liver by penetration of fractured ribs. However, liver ruptures without rib cage fractures were found in autopsies in a series of cases.

Thioredoxin and thioredoxin reductase control tissue factor activity by thiol redox-dependent mechanism.

Abnormally enhanced tissue factor (TF) activity is related to increased thrombosis risk in which oxidative stress plays a critical role. Human cytosolic thioredoxin (hTrx1) and thioredoxin reductase (TrxR), also secreted into circulation, have the power to protect against oxidative stress. However, the relationship between hTrx1/TrxR and TF remains unknown.

Molecular bases of thioredoxin and thioredoxin reductase-mediated prooxidant actions of (-)-epigallocatechin-3-gallate.

Thioredoxin (Trx) and thioredoxin reductase (TrxR) function as antioxidant and anti-apoptotic proteins, which are often up-regulated in drug-resistant cancer cells. (-)-epigallocatechin-3-gallate (EGCG) is a naturally occurring antioxidant in green tea, but also exhibits prooxidant and apoptosis-inducing properties. We have previously showed a linkage between EGCG-induced inactivation of TrxR and decreased cell survival, revealing TrxR as a new target of EGCG.

Decreased serum levels of thioredoxin in patients with coronary artery disease plus hyperhomocysteinemia is strongly associated with the disease severity.

Objective: Elevation of homocysteine and thioredoxin (Trx) levels was found in some patients with coronary artery diseases (CAD). However, their correlations with CAD were not clear. Dysfunction of thioredoxin/thioredoxin reductase (TrxR) may cause oxidative stress that is common to CAD.

Opposing regulation of histamine-induced calcium signaling by sodium selenite and ebselen via alterations of thiol redox status.

Elevated blood histamine plays a role in the pathogenesis of atherosclerosis. Calcium signaling mediates histamine action in endothelial cells. Selenium (Se) is a dietary essential trace element for humans.

Penultimate selenocysteine residue replaced by cysteine in thioredoxin reductase from selenium-deficient rat liver.

Selenium is an essential micronutrient for humans and animals, and its deficiency can predispose to the development of pathological conditions. This study evaluates the effect of selenium deficiency on the thioredoxin system, consisting of NADPH, selenoprotein thioredoxin reductase (TrxR), and thioredoxin (Trx); and the glutathione system, including NADPH, glutathione reductase, glutathione, and glutaredoxin coupled with selenoprotein glutathione peroxidase (GPx). We particularly investigate whether inactive truncated TrxR is present under selenium-starvation conditions due to reading of the UGA codon as stop.

Systematic characterization of the covalent interactions between (-)-epigallocatechin gallate and peptides under physiological conditions by mass spectrometry.

(-)-Epigallocatechin gallate (EGCG) is a major bioactive component in leaves of green tea, and has been widely investigated for its anti-tumor activity. The interaction between EGCG and the key peptides or proteins (e.g.

Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions.

Black tea is recently reported to have anti-carcinogenic effects through pro-oxidant property, but the underlying mechanisms remain unclear. Mammalian cytosolic thioredoxin reductase (TrxR1) is well -known for its anti-oxidation activity. In this study, we found that black tea extract (BTE) and theaflavins (TFs), the major black tea polyphenols, inhibited the purified TrxR1 with IC(50) 44 microg/ml and 21+/-1 microg/ml, respectively.

Inhibitory effect of green tea extract and (-)-epigallocatechin-3-gallate on mammalian thioredoxin reductase and HeLa cell viability.

Mammalian cytosolic thioredoxin reductase (TrxR1) is an attractive target for developing cancer chemopreventive agents since its inhibition is associated with a reduced growth of cancer cells. However, the known inhibitors of this enzyme mostly have a toxic effect on human health. We report on a non-toxic inhibitor, green tea.

Ebselen: a thioredoxin reductase-dependent catalyst for alpha-tocopherol quinone reduction.

The thioredoxin system, composed of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, is a powerful protein disulfide reductase system with a broad substrate specificity. Recently the selenazol drug ebselen was shown to be a substrate for both mammalian TrxR and Trx. We examined if alpha-tocopherol quinone (TQ), a product of alpha-tocopherol oxidation, is reduced by ebselen in the presence of TrxR, since TQ was not a substrate for the enzyme itself.

Effect of selenium-supplement on the calcium signaling in human endothelial cells.

Intracellular Ca2+ signaling controls many cellular functions. Understanding its regulation by selenoproteins is essential for understanding the role of selenoproteins in regulating cell functions. The activity of thioredoxin reductase (TrxR), thioredoxin (Trx) content, and the activity of glutathione peroxidase (GPx) in the human endothelial cells cultured in selenium-supplemented medium (refer as Se+ cells) was found 70%, 40%, and 20% higher, respectively than those in the cells cultured in normal medium (refer as Se0 cells).