Disease relevance of Txn1

• Experimental hyperthermia induced impairment of ADF/cofilin phosphorylation and the formation of intranuclear cofilin inclusions in mutant germ cells [1].
• Trx transgenic (Tg) mice are more resistant to cerebral infarction and survive longer than wild-type (WT) C57BL/6 mice [2].
• Thioredoxin was first isolated as a hydrogen donor for enzymatic synthesis of deoxyribonucleotides by ribonucleotide reductase in Escherichia coli [3].
• Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1 [4].
• The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress [4].
• Overexpression of TRX-1 also attenuated pancreatic fibrosis and suppressed the activation of pancreatic stellate cells [5].

Psychiatry related information on Txn1

• Moreover, to clarify the difference between the embryo-protecting mechanisms of TRX and SOD, as well as the critical periods of their actions, we carried out experiments in which we transferred embryos among three different media: basic, TRX- and SOD-supplemented [6].

High impact information on Txn1

• The data suggest that TXNIP and TRX are key components of biomechanical signal transduction and establish them as potentially novel regulators of TNF signaling and inflammation in ECs [7].
• Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy [8].
• The 17-beta estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro [9].
• Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline [8].
• Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells [8].

Chemical compound and disease context of Txn1

• Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice [8].
• Previously, we have shown that dexamethasone, a synthetic glucocorticoid, causes a down-regulation of several antioxidant defense enzymes and proteins, including catalase and thioredoxin, concomitant with the induction of apoptosis in WEHI7.2 mouse thymoma cells [10].
• Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice [11].
• Transfection of mouse WEHI7.2 lymphoma cells with human TrxP-1 or TrxP-2, but not TrxP-4, protects the cells against H(2)O(2) induced apoptosis but does not protect against apoptosis induced by dexamethasone, etoposide, or doxorubicin [12].

Biological context of Txn1

• Absolute gene expression patterns of thioredoxin and glutaredoxin redox systems in mouse [13].
• Mouse thioredoxin gene maps on chromosome 4, whereas its pseudogene maps on chromosome 1 [14].
• Compounds with up to two carbon-gold bonds were often potent inhibitors of TrxR with IC50 values as low as 2 nmol/l. In the presence of Trx and insulin the inhibiting capacity was much lower [15].
• Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function [16].
• RESULTS: Upregulation of TRX and HNE-modified protein, decrease of GSH, and nuclear translocation of NF-kappaB were noted after light exposure in PBS-treated mice [17].

Anatomical context of Txn1

• Studies with human thioredoxin-1 (Trx-1)-transgenic (Tg) mice were conducted to evaluate the relationship between stimulation of T-cell mitogenic response by sodium selenite and the intracellular Trx-1 levels, and the activities of selenoenzymes and NF-kappaB-DNA binding [18].
• Immunohistochemical localization of thioredoxin and glutaredoxin in mouse embryos and fetuses [19].
• LIM kinase 1 regulates actin filament dynamics through inhibition of ADF/cofilins [20].
• We conclude that the rapid E2-mediated activation of the Txn pathway is an important step in the response of the mammalian uterus to estrogen [21].
• Our results provide strong genetic evidence that LIMK and its substrate ADF/cofilin are involved in spine morphology and synaptic properties and are consistent with the notion that the Rho family small GTPases and the actin cytoskeleton are critical to spine structure and synaptic regulation [22].

Associations of Txn1 with chemical compounds

• Both microvessel and parenchymal TRx 1 levels were increased by hyperoxia; however, the microvascular response was limited and delayed in comparison to that of the parenchymal fraction [23].
• CONCLUSIONS: Retinal redox status is altered by intense light and is normalized partially by the effect of NAC on TRX and GSH tissue levels [17].
• Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems [24].
• TGR can reduce Trx, GSSG, and a GSH-linked disulfide in in vitro assays [24].
• Rather, reduced ROCKII expression and attenuated phosphorylation of ADF/cofilin on serine 3 occurred [25].

Physical interactions of Txn1

• These results suggest that the stimulation of T-cell mitogenic response by the physiological levels of selenite is predominantly caused by increased TR activity, which may lead to reduction of Trx-1 dependent on the intracellular expression level and promotion of DNA binding of NF-kappaB [18].

Regulatory relationships of Txn1

• Biochemical analysis showed that mVDUP1 inhibited the insulin-reducing activity of TRX [16].
• Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis [26].
• Overexpression of thioredoxin inhibited tumor necrosis factor-alpha-induced apoptosis of HepG2 cells [11].
• Addition of thioredoxin to preincubation media did not affect the percentage of motility and the fertilization rate but increased the rate of blastocyst formation to an extent similar to that triggered by catalase (2.7- and 3.3-fold, respectively) [27].

Other interactions of Txn1

• Txn maps to Chr 4, whereas Txn-ps1 maps to the proximal region of Chr 1 [14].
• 5. In some fetal organs like the liver, pancreas and kidney, TRX and GRX showed heterogeneous localization, suggesting that their expression may reflect the variable functional states of the cell [28].
• TRX is known to interact with other proteins such as proliferation-associated gene and apoptosis signal-regulating kinase 1 [16].
• Taken together, these results demonstrate that mVDUP1 functions as an oxidative stress mediator by inhibiting TRX activity [16].
• Lens-specific regulation of the thioredoxin-1 gene, but not thioredoxin-2, upon in vivo photochemical oxidative stress in the Emory mouse [29].

Analytical, diagnostic and therapeutic context of Txn1

• These findings should help to understand Txn itself, and provide a basis for transgenic experiments by gene targeting [30].
• We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-beta estradiol [9].
• Complete genomic microarray analysis revealed that M. tuberculosis sigH may mediate the transcription of at least 31 genes directly and that it modulates the expression of about 150 others; the SigH regulon governs thioredoxin recycling and may be involved in the maintenance of intrabacterial reducing capacity [31].
• Similarly, thioredoxin-overexpressing WEHI7.2 cells, shown previously to be apoptosis resistant, showed decreased cell death in tumor xenografts [10].
• The contents of GSH and TRX were significantly decreased by MPTP treatment in comparison with those of the control group [32].

References