NFE2L2 regulates the expression of TXN (Thioredoxin) by binding to ARE element present on TXN promoter and regulating anti-oxidant response (Hawkes et al, 2014; Tanito et al, 2005; Kim et al, 2001).
NFE2L2 regulates the expression of TXN (Thioredoxin) by binding to ARE element present on TXN promoter confirmed through ChIP and EMSA assay in K562 cells (Hawkes et al, 2014; Tanito et al, 2005; Kim et al, 2001).
Thioredoxin (TXN) reduces oxidized FOXO4 and disrupts interaction between FOXO4 and EP300 (p300). TXN-mediated disruption of FOXO4:EP300 complexes is negatively regulated by TXNIP (TBP-2), a TXN binding protein (Dansen et al. 2009).
Recombinant human thioredoxin (TXN) reduces oxidized recombinant mouse Foxo4 and disrupts interaction between Foxo4 and recombinant human EP300. TXN-mediated disruption of Foxo4:EP300 complexes is negatively regulated by recombinant human TXNIP (TBP-2), a TXN binding protein (Dansen et al. 2009).
Peroxiredoxin 1 (PRDX1), PRDX2, and PRDX5 in the cytosol reduce hydrogen peroxide (H2O2) with thioredoxin yielding oxidized thioredoxin and water (Yamashita et al. 1999, Lee et al. 2007, Nagy et al. 2011).
Peroxiredoxin 5 (PRDX5) very efficiently reduces peroxynitrite using thioredoxin to yield nitrite (NO2-), water, and oxidized thioredoxin (Dubuisson et al. 2004). The N-terminal cysteine (Cys 47) of PRDX5 attacks the O-O peroxide bond of peroxynitrite.
Thioredoxin reductase 2 (TXNRD2) in the mitochondrial matrix regenerates reduced thioredoxin (TXN) by reacting oxidized thioredoxin with NADPH (Gasdaska et al. 1999, Cao et al. 2007).
Peroxiredoxin 3 (PRDX3) and PRDX5 in the mitochondrial matrix reduce hydrogen peroxide (H2O2) with thioredoxin to yield oxidized thioredoxin and water (Yamashita et al. 1999, Knoops et al. 1999, Cao et al. 2007, Nagy et al. 2011). Reduced PRDX5 is a monomer (Declercq et al. 2001) and oxidized PRDX5 is a dimer (Evrard et al. 2004) therefore the enzyme may cycle between states.
Thioredoxin-interacting protein (TXNIP) binds NLRP3. Reactive oxygen species (ROS) such as H2O2 increase this interaction, while the ROS inhibitor APDC blocks it (Zhou et al. 2010). This interaction is proposed to activate the NLRP3 inflammasome.
Heme oxygenase (HMOX1), besides its enzymatic activity of the dimeric membrane protein isoform, also occurs as soluble cytosolic protein. It is probably this form that binds to the NACHT domain of NLRP3, suppressing production of epithelial cell-derived cytokines induced by activation of the NLRP3 inflammasome, and protecting airway epithelium in asthma (Lv et al, 2018).
TXNIP interacts with the redox-active domain of thioredoxin (TRX) and is believed to act as an oxidative stress mediator by inhibiting TRX activity or by limiting its bioavailability (Nishiyama et al. 1999, Liyanage et al. 2007).
ROS induce the dissociation of TXNIP from thioredoxin, freeing TXNIP to subsequently bind NLRP3 and bring about activation of the NLRP3 inflammasome (Zhou et al. 2010).
Thioredoxin reductase 1 (TXNRD1) homodimer is involved in the reduction of methylseleninic acid (MeSeO2H) into methylselenenic acid (MeSeOH) (Gromer and Gross 2002).
Thioredoxin reductase 1 (TXNRD1) homodimer is involved in the reduction of methylselenenic acid (MeSeOH) into methylselenol (MeSeH) (Gromer and Gross 2002).
Thioredoxin reductase 1 (TXNRD1) homodimer (Sun et al. 1999) is involved in the reduction of selenite (SeO3(2-)) into hydrogen selenide (H2Se). This reaction is inferred from the event in cow (Kumar et al. 1992).
A polysulfur chain may be produced at the catalytic site of CysS248-MPST. H2Sn is released after CysS248-MPST binds mitochondrial thioredoxin (TXN2) (Smeets et al. 2005, Yadav et al. 2013, Holzerova et al. 2016). The length of the sulfur chain released from MPST may vary depending on the availability of thioredoxin (Kimura 2016). When the interaction between MPST and thioredoxin is strong, the shorter form H2S can be released.
TXNRD1 expression is regulated downstream of the KEAP1-NFE2L2 pathway in response to oxidative and electrophilic stress (Kwak et al, 2003; Kim et al, 2001; Malhotra et al, 2010; reviewed in Baird and Yamamoto, 2020). NFE2L2 binds the antioxidant response element (ARE) as assessed by ChIP in mouse studies. Expression of TXNRD1 is significantly upregulated in the absence of KEAP1, marking it as an inducible NFE2L2 target gene (Malhotra et al, 2010). Binding and transcriptional activation by NFE2L2 at the TXNRD1 promoter is enhanced by CREBBP- or EP300-mediated acetylation of NFE2L2 at 18 residues in the N-terminal Neh1 domain (Sun et al, 2009).
Peroxiredoxin 5 (PRDX5) very efficiently reduces peroxynitrite using TXN2 in mitochodria to yield nitrite (NO2-), water, and oxidized TXN2 (Dubuisson et al. 2004). The N-terminal cysteine (Cys 47) of PRDX5 attacks the O-O peroxide bond of peroxynitrite.
TXNRD1 gene expression is upregulated in response to oxidative and electrophilic stressors in a way that depends on the KEAP1-NFE2L2 pathway (Kwak et al, 2003; Kim et al, 2001; Malhotra et al, 2010; reviewed in Baird and Yamamoto, 2020).
When in reduced form, TXN (thioredoxin) binds the amino terminus of MAP3K5 (ASK1) and inhibits its kinase activity. Once reactive oxygen species (ROS) oxidize TXN, TXN dissociates from MAP3K5, enabling MAP3K5 to phosphorylate downstream targets (Saitoh et al. 1998). Increased expression and activity of MINK1 (MINK) (and possibly other Ste20 family kinases TNIK and MAP4K), which is induced by ROS generated as a consequence of oncogenic RAS signaling, may contribute to MAP3K5 activation (Nicke et al. 2005).
Prostamide/prostaglandin F synthase, FAM213B and thioredoxin (TXN) are the proteins involved in the reduction of prostaglandin H2 (PGH2) to prostaglandin F2alpha (PGF2a) (Moriuchi et al. 2008, Yoshikawa et al. 2011). This reaction has been inferred from an event in mice. An additional way of achieving this reaction involves the protein aldo-keto reductase family 1 member C3 (AKR1C3) aka PGFS.