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Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Gene References into Functions
this study shows that miR-125a suppressed TrxR1 expression by targeting its 3'-UTR in endothelial cells PMID: 30225271
In human colonic epithelial cells, significant upregulation of NAD(P)H dehydrogenase [quinone] 1 (up to threefold) and thioredoxin reductase 1 (up to twofold) by 10muM sulforaphane (from broccoli), 5muM carnosol (rosemary), and 20muM cinnamaldehyde (cinnamon) was observed. PMID: 28688915
These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulation. PMID: 27346647
However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor kappaB (NF-kappaB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells. PMID: 28471109
Multivariate analysis found TXNRD1 was an independent prognostic factor for hepatocellular carcinoma (HCC)patients. In conclusion, our data suggested that TXNRD1 was a biomarker for the prognosis of patients with HCC. PMID: 28536696
Mechanistic study uncovers for the first time that the selenoprotein thioredoxin reductase (TrxR) is one of the targets by which PL-CL promotes the ROS generation PMID: 27233942
Endogenous TrxR1 is sensitive to nitrosylation-dependent inactivation. PMID: 27377780
This study thus provides novel insights into the catalytic mechanisms of TrxR1. One-electron juglone reduction by TrxR1 producing superoxide should furthermore contribute to the well-known prooxidant cytotoxicity of juglone PMID: 26898501
Mutation of TXNRD1 was identified in a family with genetic generalized epilepsy. PMID: 28232204
Data show that small molecule B19 targets and inactivates thioredoxin reductase 1 (TrxR1) in gastric cancer cells. PMID: 26919094
High TRXR1 expression is associated with oral squamous cell carcinoma. PMID: 28653098
Inhibition of thioredoxin reductase-1 by brevetoxin-2 is via the formation of a Michael adduct between selenocysteine and the alpha, beta-unsaturated aldehyde moiety of the toxin. PMID: 28551108
Here, the authors use a novel assay to demonstrate that the reduction in non-native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). PMID: 28093500
Taken together, these findings indicate that auranofin inhibition of TrxR activity in Hep3B cells activates ROS- and caspase-dependent apoptotic signaling pathways and triggers cancer cell death. PMID: 28218611
It was observed that the combination of redox/protonation states of the N-terminal (FAD and Cys59/64) and C-terminal (Cys497/Selenocysteine498) redox centers defines the preferred relative positions and allows for the flexible arm to work as the desired electron "shuttle." PMID: 27667125
Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. PMID: 27381867
thioredoxin reductase is inhibited by plumbagin, which leads to apoptosis in HL-60 cells PMID: 28249720
TXNRD1 variants may favor anti-tuberculosis drug-induced hepatotoxicity susceptibility in females and nonsmokers. PMID: 27706680
Our findings demonstrate that elevated TrxR1 levels correlate with the acquisition of bortezomib resistance in MM. We propose considering TrxR1-inhibiting drugs, such as auranofin, either for single agent or combination therapy to circumvent bortezomib-resistance and improve survival outcomes of MM patients. PMID: 26743692
Cardamonin exposure and selenium availability regulate expression of HO-1, GPX2 and TrxR1 in human intestinal cells. PMID: 26698667
Under the conditions of inhibition of TrxRs in cells, Parthenolide (PTL) does not cause significant alteration of cellular thiol homeostasis, supporting selective target of TrxRs by PTL. Importantly, overexpression of functional TrxR1 or Trx1 confers protection, whereas knockdown of the enzymes sensitizes cells to PTL treatment. PMID: 27002142
TXNRD1_v1 and TXNRD1_v2 have distinct roles in differentiation, possibly by altering the expression of the genes associated with differentiation, and further emphasize the importance in distinguishing each unique action of different TrxR1 splice forms PMID: 26464515
Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. PMID: 26184858
Rheumatoid arthritis patients with high disease activity had significantly elevated TrxR levels in plasma and synovial fluid than did those with low disease activity. PMID: 26871773
TRX-1/PRX-1 levels are associated with NADPH oxidase-activity in vivo and in vitro in atherosclerosis. PMID: 26117319
It seems to be involved in the malignant progression of meningiomas. PMID: 25592259
The association of TXNRD1 variability was found with physical performance, with three variants (rs4445711, rs1128446, and rs11111979) associated with physical functioning after 85 years of age. PMID: 26064428
In gene-based analysis of Se metabolism and selenoprotein candidate genes, only thioredoxin reductase 1 (TXNRD1) was significantly associated with toenail Selenium levels. [meta-analysis] PMID: 25343990
Expression of TrxR1 correlated highly with both the astrocytoma grade and proliferative index PMID: 25391969
Thioredoxin reductase activity may be more important than GSH level in protecting human lens epithelial cells against UVA light. PMID: 25495870
Thioredoxin reductase 1 (TrxR1) protein levels and activity were inducible up to 2.2-fold by selenium. PMID: 25179160
Data suggest TXNRD1 and TXRNRD2 function at the top of a redox pyramid that governs the oxidation state of peroxiredoxins and other protein factors, thereby dictating a hierarchy of phenotypic responses to oxidative insults. PMID: 24624337
Targeting TrxR1 with shikonin thus discloses a previously unrecognized mechanism underlying the biological activity of shikonin and provides an in-depth insight into the action of shikonin in the treatment of cancer. PMID: 24583460
Targeting of TrxR1 by GA thus discloses a previously unrecognized mechanism underlying the biological action of GA and provides useful information for further development of GA as a potential agent in the treatment of cancer. PMID: 24407164
Sec-containing TrxR1 is absolutely required for self-sufficient growth of MEFs under high-glucose conditions, owing to an essential importance of this enzyme for elimination of glucose-derived H2O2. PMID: 24853413
The oxidoreductase activities of TRP14 thereby complement those of Trx1 and must therefore be considered for the full understanding of enzymatic control of cellular thiols and nitrosothiols. PMID: 24778250
These findings suggest that high levels of TrxR may be related to progression of glioblastoma multiforme PMID: 23512591
Increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with varicocele. PMID: 23603921
v3 is an intricately regulated protein that expands TXNRD1-derived protein functions to the membrane raft compartment PMID: 23413027
Data suggest that dietary factor (selenium supplementation) up-regulates endogenous antioxidant systems and protects trophoblasts from oxidative stress; selenium upregulates GPX1 (glutathione peroxidase 1) and thioredoxin reductases (TXNRD1; TXNRD2). PMID: 23063346
Our study suggests a novel interaction of up-regulated TXN-TXNRD1 system-mediated oxidative stress defense mechanisms and down-regulated angiogenesis pathways as an adaptive response in obese nondiabetic subjects. PMID: 21593104
study reveals significant differences between TrxR1 and TrxR2 in substrate specificity and metal compound inhibition in vitro and in cells PMID: 21172426
Overexpression of TrxR1 could contribute to cancer progression and might be a potential molecular marker for therapy. PMID: 21206984
These results indicate the ability of TR1 to modulate the cytotoxic effects of selenium compounds in human lung cancer cells through mitochondrial dysfunction. PMID: 20920480
High expression of TXNRD1 is associated with breast cancer. PMID: 20584310
High levels of expression in lung carcinoma cells modulate drug-specific cytotoxic efficacy PMID: 19766715
Results show the critical role of TxnRd1 in curcumin-mediated radiosensitization and suggest that TxnRd1 levels in tumors could have clinical value as a predictor of response to curcumin and radiotherapy. PMID: 20160040
Class-I pyridine nucleotide-disulfide oxidoreductase family
Tissue Specificity
Isoform 1 is expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus,