Disease relevance of PRDX2

• Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, is under-expressed in Down syndrome fetal brains [1].
• To test whether decreased expression is associated with enhanced sensitivity of DS neurons to reactive oxygen species, we down-regulated PRDX2 through stable transfections of SH-SY5Y neuroblastoma cells with antisense contructs of the complete PRDX2 coding sequence [1].
• Human AOEB166 shares 63% similarity with Escherichia coli AhpC22 alkyl hydroperoxide reductase and 66% similarity with a recently identified Saccharomyces cerevisiae alkyl hydroperoxide reductase/thioredoxin peroxidase [2].
• The rat and yeast TSA proteins show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity [3].
• Recombinant NKEF-A and NKEF-B inhibited HIV-1 replication when exogenously added to acutely infected T-cells at an ID(50) (dose inhibiting HIV-1 replication by 50%) of approximately 130 nm (3 microg/ml) [4].

Psychiatry related information on PRDX2

• Two-hundred and seventy-one 11- and 12-year-olds, with elevated depressive symptoms, were randomized to PRP or usual care [5].
• Most importantly we found that in addition to increased abnormalities with increasing substance use disorder the PI/SD group had significantly more abnormalities compared to the PI group with regard to both the TSA (P < .05) and AVBIT (P < .05) composite parameters as meas[6]
• PRP did not significantly prevent depressive disorders but significantly prevented depression, anxiety, and adjustment disorders (when combined) among high-symptom participants [5].
• METHODS: Pain thresholds were examined with a psychophysical computerized quantitative thermal sensory testing device (TSA 2001) in healthy volunteers recruited from three different Asian ethnic groups [7].

High impact information on PRDX2

• As shown by mobility-shift, methylation interference, and mutational analyses, the mammalian protein BSAP recognizes all four sea urchin binding sites in a manner indistinguishable from TSAP; however, the two proteins differ in molecular weight [8].
• Thus, immunoselection mediated by T lymphocytes during metastasis formation could be directed against both MHC and TSA antigens [9].
• Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C [10].
• Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes [3].
• A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA [3].

Chemical compound and disease context of PRDX2

• Corepressor proteins often have associated histone deacetylases (HDAC) and reflectively the antiproliferative action of 1alpha,25(OH)2D3 can be 'restored' by cotreatment with low doses of HDAC inhibitors such as trichostatin A (TSA, 15 nM) to induce apoptosis in prostate cancer cell lines [11].
• A total of 281 Staphylococcus aureus strains selected from those submitted to the Centers for Disease Control for phage typing between 1956 and 1982 were tested for the production of toxic-shock-associated protein (TSAP) by isoelectric focusing (IEF) and solid-phase radioimmunoassay [12].
• According to the preventative heparin dose schedule based on the TFA measured by the TSA, all disseminated intravascular coagulation (DIC) was controlled successfully [13].
• Here we showed that HDAC inhibitors sodium butyrate, TSA, and valproate regulated the expression of Interleukin-18 (IL-18), a cytokine with antitumor and proinflammatory properties, in human acute myeloid leukemia cell lines U937 and HEL [14].
• METHODS AND RESULTS: Predictive power of TSA was investigated in the placebo arm of the European Myocardial Infarction Amiodarone Trial, which enrolled patients surviving acute myocardial infarction with left ventricular ejection fraction (LVEF) < or =40% [15].

Biological context of PRDX2

• The protein contains three motifs that are highly conserved within the TSA family, including a cysteine residue that is the active site of oxidation for this class of proteins [16].
• Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress [17].
• Abrin triggers cell death by inactivating a thiol-specific antioxidant protein [18].
• Based on PCR analysis of DNA from a human/rodent somatic cell hybrid panel, the TDPX1 locus was assigned to chromosome 13 [19].
• It was also determined by PCR analysis of various YACs that the TDPX1 locus is in the region of the dinucleotide repeat markers D13S289 and D13S290 [19].

Anatomical context of PRDX2

• SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria [20].
• From these results we concluded that SP-22 is thioredoxin-dependent peroxide reductase or so-called thioredoxin peroxidase in mitochondria from the adrenal cortex [20].
• T-cells transfected with NKEF-A or NKEF-B cDNA were able to inhibit 80-98% HIV-1 replication in vitro [4].
• HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family [4].
• Peroxiredoxin 5 (PRDX5) is a novel type of mammalian thioredoxin peroxidase widely expressed in tissues and located cellularly to mitochondria, peroxisomes and cytosol [21].

Associations of PRDX2 with chemical compounds

• In contrast to TPx, in which one of the two conserved cysteines is oxidized to Cys-SOH and then immediately reacts with the second conserved cysteine of the second subunit of the enzyme homodimer to form an intermolecular disulfide, the Cys-SOH of 1-Cys Prx does not form a disulfide [22].
• The thiol specificity of the protective activity of TSA derives from the fact that the oxidized form of TSA can be converted back to its sulfhydryl form by treatment with thiols but not by ascorbate [23].
• The thiol-specific antioxidant protein (TSA) protects glutamine synthetase from inactivation by a metal-catalyzed oxidation (MCO) system comprised of dithiothreitol (DTT)/Fe3+/O2 but not by the ascorbate/Fe3+/O2 MCO system [23].
• Like catalase, TSA prevents the initiation of the rapid O2 uptake phase during MCO of DTT but causes only partial inhibition when added after the reaction is well into the propagation phase [23].
• Reduced thioredoxin serves as an electron donor for thioredoxin peroxidase (TPx) which consequently reduces H(2)O(2) to H(2)O [24].
• These results demonstrate that peroxiredoxin 2 has a tertiary structure that facilitates reaction of the active site thiol with hydrogen peroxide while restricting its reactivity with other thiol reagents [25].

Regulatory relationships of PRDX2

• Also, expression of peroxiredoxin 2 was up-regulated in RA [26].

Other interactions of PRDX2

• The protein is homologous to thioredoxin peroxidase and other antioxidant proteins [20].
• This suggests that the decreased expression of PRDX2 may contribute to the altered redox state in DS at levels comparable to that of the increased expression of SOD1 [1].
• Elevated plasma levels of both NKEF-A and NKEF-B proteins were detected in 23% of HIV-infected non-treated individuals but not in persons treated with highly active antiviral therapy or uninfected persons [4].
• This regional mapping localizes the TDPX1 gene to a genomic region recently shown to contain the breast cancer susceptibility gene BRCA2 and a gene associated with a form of muscular dystrophy [19].
• Thioredoxin peroxidase (natural killer enhancing factor) regulation of activator protein-1 function in endothelial cells [27].

Analytical, diagnostic and therapeutic context of PRDX2

• The under-expression of PRDX2 observed in DS samples was confirmed by real-time PCR (0.73-fold) [1].
• Further localization of the locus to 13q12 was accomplished by fluorescence in situ hybridization analysis, using as a probe DNA from a yeast artificial chromosome (YAC) that contains the TDPX1 gene [19].
• These results demonstrate that the NKEF-B is an antioxidant that protects cells from oxidative stress, chemotherapy agents, and inflammation-induced monocyte adhesion [28].
• Using direct sequencing procedures (Edman degradation) or matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), these four spots were identified as three new proteins: thioredoxin peroxydase 1 (TDPX1), transthyretin (TTR) and retinol-binding protein (RBP) [29].
• H2O2, and TNF-a, and TSA all increased NF-kappaB and AP-1 DNA binding to their consensus sites assessed by the electrophoretic mobility shift assay [30].

References