Disease relevance of Glrx

• Mouse glutaredoxin - cDNA cloning, high level expression in E. coli and its possible implication in redox regulation of the DNA binding activity in transcription factor PEBP2 [1].
• Pretreatment with alpha-lipoic acid, a thiol delivery agent that protects motor neurons from L-BOAA-mediated toxicity prevented the upregulation of thioltransferase and AP1 activation, presumably by maintaining thiol homeostasis [2].

High impact information on Glrx

• PICOT-HD: a highly conserved protein domain that is often associated with thioredoxin and glutaredoxin modules [3].
• With this method, glutaredoxin, monitored by Western blot, was knocked out by overexpressing 290-base sense and antisense RNA in NIH 3T3 cells controlled by tetracycline or doxycycline [4].
• This unusual substrate specificity is achieved by an evolutionary conserved fusion of the TR and glutaredoxin domains [5].
• Absolute gene expression patterns of thioredoxin and glutaredoxin redox systems in mouse [6].
• To determine the immunological consequence of pharmacological disruption of endogenous redox regulation, we used a selenium-containing antioxidant compound ebselen known to modulate both thioredoxin and glutaredoxin pathways [7].

Biological context of Glrx

• We have isolated a cDNA encoding glutaredoxin (GRX) from a mouse splenic cDNA library [1].
• These results suggest that TRX and GRX play some tissue-specific roles in mammalian morphogenesis as well as general roles as antioxidant enzymes [8].
• We also found that the C-terminal penultimate selenocysteine was required for transfer of reducing equivalents from the thiol/disulfide active site of TGR to the glutaredoxin domain [9].
• We have previously characterized a T. cruzi virulence factor named Tc52 sharing structural and functional properties with the thioredoxin and glutaredoxin protein family [10].
• Thioltransferase (or Grx) belongs to the oxidoreductase family and is known to regulate redox homeostasis in cells [11].

Anatomical context of Glrx

• In contrast, there was no increase of GRX mRNA in D-cell, which is a sub-cell line derived from M1 lacking in the capacity of differentiation [12].
• GRX mRNA also increased in U937 cells differentiated by phorbol 12-myristate 13-acetate (PMA) [12].
• Immunohistochemical localization of thioredoxin and glutaredoxin in mouse embryos and fetuses [8].
• It inhibits mitochondrial complex I in motor cortex and lumbosacral cord of male mice through oxidation of critical thiol groups, and glutaredoxin, a thiol disulfide oxido-reductase, helps maintain integrity of complex I. Since incidence of neurolathyrism is less common in women, we examined the mechanisms underlying the gender-related effects [13].
• Thioltransferase (glutaredoxin) mediates recovery of motor neurons from excitotoxic mitochondrial injury [2].

Associations of Glrx with chemical compounds

• While not active in redox reaction and glutathione binding, SH3BGRL3 may act as an endogenous modulator of glutaredoxin activities by competing, with its fully conserved thioredoxin fold, for binding to yet unknown target proteins [14].
• Higher constitutive expression of glutaredoxin could potentially contribute to the neuroprotection seen in female mouse following exposure to neurotoxins, such as MPTP [15].
• Estrogen and neuroprotection: higher constitutive expression of glutaredoxin in female mice offers protection against MPTP-mediated neurodegeneration [15].
• A thiol/disulfide oxidoreductase component of the GSH system, glutaredoxin (Grx), is involved in the reduction of GSH-based mixed disulfides and participates in a variety of cellular redox pathways [16].
• Mice treated with acetaminophen exhibited decreased glutathione peroxidase activity, decreased thioltransferase activity, and decreased adenine nucleotide concentrations in the liver [17].

Physical interactions of Glrx

• This showed that GRX may be involved in the redox regulation of the DNA-binding activity of PEBP2 as is the case with thioredoxin [1].

Regulatory relationships of Glrx

• Furthermore, glutaredoxin activity in female mice was down-regulated by estrogen antagonist indicating its regulation by estrogen receptor [13].

Other interactions of Glrx

• In electrophoretic mobility shift assay, we proved that wild type GRX, not mutant one, recovered the DNA-binding activity of a transcription factor, PEBP2, oxidized by diamide [1].
• By comparison, in Gpx1-deficient mice, the expression of antioxidant genes was unaltered except for a decrease in glutaredoxin-1 and an increase in glutaredoxin-2 [18].
• An increase in glutathione reductase and thioltransferase activities was observed after BHA, PB or CAF treatment; glyoxalase I and Se-dependent glutathione peroxidase were depressed in comparison with the control group in all cases studied [19].
• Down-regulation of glutaredoxin by estrogen receptor antagonist renders female mice susceptible to excitatory amino acid mediated complex I inhibition in CNS [13].

References