Disease relevance of Txn1

• Thioredoxin-interacting protein controls cardiac hypertrophy through regulation of thioredoxin activity [1].
• Alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes is mediated via thioredoxin-1-sensitive oxidative modification of thiols on Ras [2].
• Escherichia coli MsrA and MsrB and bovine MsrA efficiently use either Trx or DTT as reducing agents [3].
• Mutual changes of thioredoxin and nitrosothiols during biliary cirrhosis: results from humans and cholestatic rats [4].
• Comparison of thioredoxin reductases from Novikoff ascites hepatoma cells and normal liver of rats [5].

High impact information on Txn1

• The results indicate that thionein (T), which is formed when the zinc is removed from Zn-MT, can function as a reducing system for the Msr proteins because of its high content of cysteine residues and that Trx can reduce oxidized T [3].
• A heat-stable protein has been detected in bovine liver that, in the presence of EDTA, can support the Msr reaction in the absence of either Trx or DTT [3].
• To develop peptides that exhibit FSH-antagonistic activity at low concentrations, we have constructed a three-dimensional model for FSH, which is based on an alignment of both the beta and the alpha chains of glycoprotein hormones with thioredoxin, for which x-ray diffraction data are available [6].
• The angiotensin II-stimulated heparin-sensitive kinase could phosphorylate a thioredoxin fusion protein containing the entire AT1A-R cytoplasmic tail (N295 to E359), which lacks consensus phosphorylation sites for GRK1, GRK2, and GRK3 [7].
• Compared with controls, erythrocyte thioredoxin levels were higher in stage I through III PBC and lower in stage IV patients [4].

Chemical compound and disease context of Txn1

• E. coli C35S Trx, in which Cys(35) was replaced with Ser, formed some adducts with MST and activated MST after treatment with DTT [8].
• Activation of the cGMP/PKG pathway induced expression of thioredoxin and Bcl-2 that were beneficial to cortical neurons in antagonizing Abeta/ceramide toxicity [9].
• Temocapril treatment ameliorates autoimmune myocarditis associated with enhanced cardiomyocyte thioredoxin expression [10].
• These findings suggest that production of peroxynitrite is involved in HI brain injury, and that induced TRX plays a neuroprotective role against oxidative stress resulting from HI [11].

Biological context of Txn1

• In this study, we demonstrate that vitamin D(3)-up-regulated protein-1 regulates thioredoxin in conditions of biomechanical or oxidative stress and critically regulates cardiomyocyte viability [12].
• Overexpression of vitamin D(3)-up-regulated protein-1 but not of thioredoxin induced cardiomyocyte apoptosis [12].
• Vitamin D(3)-up-regulated protein-1 down-regulation by strain or hydrogen peroxide led to increased thioredoxin activity, whereas adenovirus-mediated overexpression of vitamin D(3)-up-regulated protein-1 suppressed thioredoxin activity [12].
• Nucleotide sequence of a cDNA encoding rat thioredoxin [13].
• This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL) [4].

Anatomical context of Txn1

• The Vdup1 mRNA is localized to the uterine stroma in the nonreceptive endometrium, the site of increased Txn mRNA levels during decidualization [14].
• The immunoreactivity for thioredoxin, which catalyzes protein disulfide reductions, has previously been shown to exist in nerve cells and their axons [15].
• A protein, which stimulated cholesterol 7 alpha-hydroxylase activity in the presence of glutathione or thioredoxin, was purified to apparent homogeneity from rat liver cytosol [16].
• We were particularly interested in whether ebselen was activated by mitochondrial glutathione (GSH) and thioredoxin, in determining whether an ebselen moiety could be targeted to mitochondria by conjugating it to a lipophilic cation, and in exploring the nature of ebselen binding to mitochondrial proteins [17].
• In oocytes injected with rat liver poly(A)+ RNA, high Km (i.e. type I) activity was observed when 20 mM dithiothreitol was used as the thiol cofactor, whereas Km values in the nanomolar range were noted with 0.5 mM dithiothreitol, glutathione, or a reconstituted thioredoxin cofactor system [18].

Associations of Txn1 with chemical compounds

• Here we demonstrate for the first time that cysteamine increases the expression and nuclear translocation of Egr-1, Ref-1, and Trx, and activates binding of Egr-1 to DNA [19].
• Overexpression of thioredoxin-interacting protein (Txnip), an endogenous thioredoxin inhibitor, reduced protein synthesis in response to mechanical strain (89+/-5% reduction, P<0.01), phenylephrine (80+/-3% reduction, P<0.01), or angiotensin II (80+/-4% reduction, P<0.01) [1].
• Mn-Superoxide dismutase expression was increased 13-fold, and thioredoxin level was elevated 3-fold after lipopolysaccharide challenge [20].
• However, both mutations resulted in marked decreases in Vmax values when glutathione or a reconstituted thioredoxin cofactor system were used in the assay [21].
• We propose that the NADPH/GRX/TRX redox regulation mediates a novel signaling pathway of nutrient-induced insulin secretion [22].

Physical interactions of Txn1

• The heat-stable cytosolic factor that promotes glucocorticoid receptor binding to DNA is neither thioredoxin nor ribonuclease [23].

Regulatory relationships of Txn1

• Proof that the endogenous, heat-stable glucocorticoid receptor-activating factor is thioredoxin [24].

Other interactions of Txn1

• These results also support the emerging concept that the thioredoxin inhibitor Txnip is a critical regulator of biomechanical signaling [1].
• HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity [25].
• Redox control of exocytosis: regulatory role of NADPH, thioredoxin, and glutaredoxin [22].
• Oxidative stress decreases MST activity so as to increase the amount of cysteine, a precursor of thioredoxin or glutathione, and furthermore, these cellular reductants restore the activity [26].
• CaBP1, a calcium binding protein of the thioredoxin family, is a resident KDEL protein of the ER and not of the intermediate compartment [27].

Analytical, diagnostic and therapeutic context of Txn1

• In vivo, myocardial thioredoxin activity increased 3.5-fold compared with sham controls after transverse aortic constriction (P<0.01) [1].
• Here we demonstrate the localization of thioredoxin mRNA as revealed by in situ hybridization in the rat brain [15].
• Components of the thioredoxin system were localized in normal rat kidney using immunoperoxidase techniques at the light microscopic level and immunogold techniques at the ultrastructural level [28].
• Northern blot analysis showed that total TRX mRNA in the operated hemispheres was induced from 8 hours and increased until 24 hours after the surgical procedures [29].
• The animals receiving E2 or a combination of E2 and DEX showed significantly increased thioredoxin mRNA levels, by 4-fold and 5-fold, respectively, as compared to the OVX control group [30].

References