Disease relevance of Txnrd1

• Lewis lung carcinoma and solid H22 hepatoma treated with 50-250 mg/kg CTX for 3 h lost TrxR activity in a dose-dependent fashion [1].
• Although NCoAs are, in general, increased in response to hypothyroidism or in states of TH resistance, SRC-1 specifically does not regulate TR isoform expression [2].
• A trans-dominant mutational strategy was used to down-regulate trypanothione reductase (TR) activity levels in Leishmania donovani, the causative agent of visceral leishmaniasis in humans [3].
• In this study, we analyzed the expression of TrxR in peripheral blood cells, tumor-transformed leukemia, and melanoma cells and found, in addition to abundant plasma membrane localization, that TrxR was released from these cells [4].
• A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coli BL21(DE3) strain [5].

High impact information on Txnrd1

• In this report, we present the structural data on a mitochondrial TrxR, TrxR2 (also known as TR3 and TxnRd2) [6].
• Thioredoxin reductase (TrxR) is an essential enzyme required for the efficient maintenance of the cellular redox homeostasis, particularly in cancer cells that are sensitive to reactive oxygen species [6].
• T3 increased metabolic rate [whole body oxygen consumption (MVO2)] in both WT and TR alpha-/- mice, but the effect in the TR alpha 1-/- mice at the highest dose was half that of the WT mice [7].
• Recombinant cells depleted of up to 85% of TR activity were significantly impaired in their ability to regenerate dihydrotrypanothione from trypanothione disulfide following oxidation with diamide [3].
• The degree of transactivation corresponds to that observed for the mutant TR delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2 [8].

Chemical compound and disease context of Txnrd1

• In the rat hepatoma cell line H4IIE, inhibition of TrxR by aurothioglucose or by 1-chloro-2,4-dinitrobenzene led to induction of HO-1 [9].

Biological context of Txnrd1

• Our results indicate that Txnrd1 plays an essential role during embryogenesis in most developing tissues except the heart [10].
• Genomic organisation and alternative splicing of mouse and human thioredoxin reductase 1 genes [11].
• RESULTS: The human TXNRD1 gene spans 100 kb of genomic DNA organised into 16 exons and the mouse Txnrd1 gene has a similar exon/intron arrangement [11].
• CTX caused a dose-dependent cellular proliferation inhibition which was positively correlated with TrxR inhibition at 3 h [1].
• Both TrxR and GPx play an important role in protecting against oxidative stress [12].

Anatomical context of Txnrd1

• In accordance with the observed growth impairment in vivo, Txnrd1-deficient embryonic fibroblasts do not proliferate in vitro [10].
• Contribution of Thioredoxin Reductase to T-Cell Mitogenesis and NF-kB DNA-Binding Promoted by Selenite [13].
• Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and the mitochondria of mammalian cells [10].
• The generation of reactive oxygen species in a human carcinoma cell line was shown to result in both the oxidation of the selenocysteine in TR1 and a subsequent increase in the expression of this enzyme [14].
• However, the relative contributions of TR isoforms in the pituitary vs. the hypothalamus remain to be completely elucidated [15].

Associations of Txnrd1 with chemical compounds

• Treatment with NF-kappaB nuclear translocation inhibitor SN50 or thioredoxin reductase (TR) inhibitor aurothioglucose depressed this stimulatory action [13].
• Cyclophosphamide as a potent inhibitor of tumor thioredoxin reductase in vivo [1].
• Mammalian thioredoxin reductase (TrxR) catalyzes the reduction of oxidized thioredoxin in a NADPH-dependent manner, and contains a selenocysteine residue near the C-terminus [12].
• Both human and mouse Grx2 showed glutathione (GSH)-dependent and thioredoxin reductase (TR)-dependent peroxidase activity [16].
• A standard norepinephrine test showed that adrenergically induced thermogenesis could not be activated normally in the TR-ablated mice [17].

Regulatory relationships of Txnrd1

• In the present study, we found that among these isozymes only TrxR1 was induced by tumor necrosis factor-alpha (TNF alpha) in vascular endothelial cells [18].

Other interactions of Txnrd1

• Quantitations reported establish differences among adult organs and embryonic stages, compare mRNA decay rates, explore the significance of alternative mRNA isoforms derived from TrxR1 and Grx2 genes, and examine the time-course expression upon superoxide stress promoted by paraquat [19].
• Gene expression analysis on the microdissected liver tissues of the mice in the DEN + DC group showed the highest expression levels of oxidative stress-related genes, such as Cyp1a1 and Txnrd1, in the tumor areas [20].

Analytical, diagnostic and therapeutic context of Txnrd1

• In this study we elucidated the genomic organisation of the mouse (Txnrd1) and human thioredoxin reductase 1 genes (TXNRD1) through library screening, restriction mapping and database mining [11].
• We found that 4 h after a bolus dose of CTX (30, 90, 150, 300 and 450 mg/kg) were administrated intraperitoneally, TrxR activity was significantly decreased in a dose-dependent manner, by 32%, 44%, 68%, 87% and 99%, respectively, in comparison with control group [12].
• Here, the major rat TrxR1 mRNA was determined as 3.5 kb by Northern blotting [21].
• By sequence determination of the rat genomic sequence upstream of the open reading frame for TrxR1, an exon was encountered that encoded a third alternative 5' UTR domain that could also be expressed, as confirmed by its presence in a mouse skin TrxR1 cDNA clone [21].
• Western blot analysis showed that the antibodies specifically bound to a 58 kDa protein, representing the subunit of TrxR [22].

References