Disease relevance of PRDX6

• Recombinant human 1-Cys Prx expressed in and purified from Escherichia coli has now been shown to reduce H2O2 with electrons provided by dithiothreitol [1].
• N-terminal sequence analysis of p29 revealed homology to an open reading frame gene described in a myeloid leukemia cell line [2].
• Saitohin, which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts with peroxiredoxin 6 [3].
• Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts [4].
• Immunohistochemical analysis in 80 breast cancer donors demonstrated a significant association of TPM4 (p = 0.002), HSP60 (p = 0.001), PDX6 (p = 0.002) but not CRAB (p = 0.113) staining with the presence of lymph node metastasis [5].

Psychiatry related information on PRDX6

• By this assay and subsequent co-immunoprecipitation and glutathione S-transferase pull-down assays, we discovered and confirmed that Saitohin interacts with peroxiredoxin 6, a unique member of that family that is bifunctional and the levels of which increase in Pick disease [3].
• Here we report the identification of a 24 kDa phosphoprotein (CSP24) associated with an intermediate stage of memory, distinct from short-term memory, detected after one-trial conditioning of Hermissenda [6].

High impact information on PRDX6

• The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals [7].
• Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C [8].
• Peroxiredoxins (Prx) are widely distributed peroxidases that can be divided into 1-Cys and 2-Cys Prx groups based on the number of conserved cysteine residues that participate in their catalytical cycle [8].
• Prx have been described to be strictly dependent on thiols, but here, we show that ascorbate (vitamin C) also reduces 1-Cys Prx, but not 2-Cys Prx, from several taxonomic groups [8].
• Reduction by ascorbate is partly related to the fact that the oxidized form of 1-Cys Prx is a stable sulfenic acid (Cys-SOH) instead of a disulfide [8].

Chemical compound and disease context of PRDX6

• A new construct which contains the His-tag plus two extra amino acids at the COOH terminus when expressed in Escherichia coli generated a protein that hydrolyzed the sn-2 acyl chain of phospholipids at pH 4, and exhibited NSGPx activity with H(2)O(2) at pH 8 [9].
• Three lines are producing IgG antibody to the 41-kDa HIV transmembrane glycoprotein gp41 and 4 produce IgG antibodies to the 24-kDa HIV core protein p24, its precursors and a breakdown product [10].
• Intriguingly, the phosphorylation of ataxia telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated cells [11].
• The 24-kDa MOMP from L. pneumophila was purified, and antibody produced to this protein cross-reacted with all species of Legionella as determined from an immunoblot of a sodium dodecyl sulfate gel [12].
• Type C1 and D toxins produced by Clostridium botulinum caused ADP-ribosylation of a protein of 24 kDa in membrane preparations of rat clonal pheochromocytoma cells (PC12) and of proteins of 25 and 26 kDa in neuron-rich culture of fetal rat brain cells [13].

Biological context of PRDX6

• Thus, LEDGF, by activating the AOP2 gene, protected and enhanced the survival of cells under oxidative stress [14].
• Finally, the GSH-mediated reduction of the disulfide regenerates the reduced active-site sulfhydryl of 1-Cys Prx [15].
• A cDNA for p29 identical to the open reading frame protein was amplified from RNA of neutrophils [2].
• By activity and sequence homology, rh-p29 can be classified as a peroxiredoxin [2].
• As for all 1-Cys peroxiredoxins identified to date, the amino acid sequence proposed to constitute the active site of the enzyme, PVCTTE, is highly conserved in XvPer1 [16].

Anatomical context of PRDX6

• Lens epithelial cells showed a higher level of AOP2 mRNA in the presence of LEDGF [14].
• Furthermore, human 1-Cys Prx transiently expressed in NIH 3T3 cells was able to remove intracellular H2O2 generated in response either to the addition of exogenous H2O2 or to treatment with platelet-derived growth factor [1].
• A 29-kDa neutrophil protein (p29) was identified by co-immunoprecipitation with p67(phox) [2].
• Finally, O(2)() production by plasma membrane and recombinant cytosolic oxidase components in the SDS-activated, cell-free NADPH oxidase system were enhanced by rh-p29 [2].
• The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene [17].

Associations of PRDX6 with chemical compounds

• Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H(2)O(2) and protect proteins and DNA from oxidative stress [14].
• We now demonstrate that a heterodimer complex is formed between 1-Cys Prx with a C-terminal His6 tag and GST pi upon incubation of the two proteins at pH 8.0 in buffer containing 20% 1,6-hexanediol to dissociate the homodimers, followed by dialysis against buffer containing 2.5 mM glutathione (GSH) but lacking 1,6-hexanediol [15].
• The heterodimer is also formed in the presence of S-methylglutathione, but no 1-Cys Prx activity is found under these conditions [15].
• Although AOP2 possesses TSA activity, it has several unique characteristics, including the absence of a second cysteine residue that is conserved in all other TSA proteins, the presence of a unique carboxy-terminal domain, and a demonstrated phospholipase activity [18].
• In addition, rh-p29 exhibited PLA(2) activity, which was Ca(2+) independent, optimal at low pH, and preferential for phosphatidylcholine substrates [2].

Physical interactions of PRDX6

• We found that LEDGF bound to the heat shock element and to stress-related elements in the AOP2 promoter [14].
• A 24-kDa heparin binding protein recently identified as tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in bovine seminal fluid was suggested to play an important role in bull fertility [19].
• The 24-kDa IGF binding protein representing IGF binding protein-4 was down-regulated in all IGF-I-treated animals, but the decrease was more marked in UN animals [20].
• However, we show that the 24 kDa protein binds coumarin drugs as tightly as the intact B protein [21].
• The drugs are known to inhibit the ATPase activity of gyrase and bind to the 24-kDa N-terminal subdomain of gyrase B protein [22].

Regulatory relationships of PRDX6

• RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death [23].
• We have cloned the gene encoding the 24-kDa protein and show that it is expressed as a 22-kDa alpha-zein with an uncleaved signal peptide [24].
• However, the IL-18 protein was expressed intracellularly and predominantly released as an unprocessed inactive 24-kDa form [25].
• Together, our results demonstrate that H2O2-mediated hyperoxidation of Prdx6 induces cell cycle arrest at the G2/M transition through up-regulation of iPLA2 activity [26].

Other interactions of PRDX6

• Among six antioxidant proteins, 1-Cys Prx showed significant increase (P > 0.05) in sCJD frontal cortex whereas Prx I was decreased (P > 0.01) [27].
• Together, these data strongly suggest that AOP2 is a novel thiol-dependent antioxidant that functions to scavenge particular hydroperoxides in the cell and mediate specific signals [18].
• In contrast, the 1-Cys Prx homodimer lacks peroxidase activity even in the presence of free GSH [15].
• Mutations in the heat shock element and stress-related elements of the AOP2 promoter reduced LEDGF-dependent trans-activation [14].
• Prxs I-IV form dimers held together by disulfide bonds, Prx V forms intramolecular bond, but the mechanism of Prx VI, so-called 1-Cys Prx, is still unclear [28].

Analytical, diagnostic and therapeutic context of PRDX6

• Rapid glutathionylation of 1-Cys Prx in the heterodimer is detected by immunoblotting [15].
• Molecular cloning of the full-length cDNA revealed a strong homology of the corresponding gene product with a bovine non-selenium glutathione peroxidase [17].
• Differential expression was confirmed for four proteins including PDX6, CRAB, TPM4, and HSP60 by real-time quantitative PCR and Western blotting analysis in our model [5].
• Randomly selected hearts from Prdx6(-/-) mice and wild-type mice were subjected to 30 min of global ischemia followed by 120 min of reperfusion at normothermia [29].
• The molecular mass of these proteins was determined to be 29 (p29) and 26 kD (p26), respectively, in SDS-PAGE [30].

References