Disease relevance of PRDX1

• 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) [1].
• In 140-d animals given lesser O(2) concentrations (as needed) that did not develop chronic lung disease, lung Prx I mRNA also was increased on Days 1 and 6, but not Day 10 [2].
• However, after premature birth (125 or 140 d gestation), lung Prx I mRNA increased rapidly with the onset of oxygen exposure [2].
• Overexpression of peroxiredoxin in human breast cancer [3].
• The absence in the pag protein of known consensus sequence, as well as its close relationship with a gene product involved in the differentiation of a mouse erythroleukemia cell line, has suggested that the PAG gene belongs to a family of genes associated with cell proliferation and differentiation [4].
• Although the cell survival-enhancing property of Prx1 has traditionally been attributed to its antioxidant activity, the reactive oxygen species-scavenging activity of Prx1 was not essential for AR stimulation because Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation [5].
• Considering the possible role of Prx1 and Nrf2 in radioresistance/chemoresistance, it warrants future investigation to evaluate whether elevated Prx1 and/or Nrf2 levels are predictive of treatment response in advanced lung cancer and other malignancies [6].

Psychiatry related information on PRDX1

• Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down syndrome [7].

High impact information on PRDX1

• Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery [8].
• We show that rice (Oryza sativa) chloroplast NADPH THIOREDOXIN REDUCTASE (NTRC), with a thioredoxin domain, uses NADPH to reduce the chloroplast 2-Cys peroxiredoxin BAS1, which then reduces hydrogen peroxide [9].
• One of the mechanisms plants have developed for chloroplast protection against oxidative damage involves a 2-Cys peroxiredoxin, which has been proposed to be reduced by ferredoxin and plastid thioredoxins, Trx x and CDSP32, the FTR/Trx pathway [9].
• Exogenously added H2O2 induced signaling in the absence of ligand, whereas catalase and a membrane-bound peroxiredoxin inhibited ligand-dependent signaling [10].
• The results showed that the level of plasma peroxiredoxin II in patients with SARS is significantly high and could be secreted by T cells [11].

Chemical compound and disease context of PRDX1

• Transfection of mouse WEHI7.2 thymoma cells with human thioredoxin peroxidase-2 was found to protect the cells from apoptosis induced by H2O2 but not from apoptosis induced by dexamethasone, doxorubicin or etoposide [12].
• These flavoproteins, designated NADH:peroxiredoxin oxidoreductases, catalyze the pyridine-nucleotide-dependent reduction of cysteine-based peroxidases (e.g. Salmonella typhimurium AhpC, a member of the peroxiredoxin family) which in turn reduce H2O2 or organic hydroperoxides [13].
• The purpose of this review is to discuss the role of endothelial-myocyte uncoupling in diabetes mellitus and increased levels of homocysteine, causing activation of latent metalloproteinases, decreased levels of thioredoxin and peroxiredoxin, and cardiac tissue inhibitor of metalloproteinase (CIMP) in response to antagonizing PPARgamma [14].

Biological context of PRDX1

• A 20-kDa binding protein was identified by the Prx VI protein overlay assay with flow-through fractions from a High-Q column with rat lung crude extracts [15].
• Peroxiredoxin V is essential for protection against apoptosis in human lung carcinoma cells [16].
• Peroxiredoxin genes exhibit thioredoxin-dependent peroxidase activity and have been implicated in a number of other cellular functions such as cell proliferation and differentiation [17].
• The acute increase in gene expression of Prx I in response to oxygen suggests an important role for this protein during the transition from relatively anaerobic fetal life to oxygen-breathing at birth [2].
• Throughout the third trimester, mRNA for Prx I was expressed constitutively at low levels in fetal baboon lung [2].

Anatomical context of PRDX1

• T-cells transfected with NKEF-A or NKEF-B cDNA were able to inhibit 80-98% HIV-1 replication in vitro [1].
• HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family [1].
• We also constructed clones of human lung epithelial cells A549 with siRNA-mediated knockdown of the PRDX5 gene [18].
• The phosphorylation of Prx I in HeLa cells was monitored with the use of antibodies specific for Prx I phosphorylated on Thr(90) [19].
• The cytosolic location of Prx I likely prevents its interaction with activated CDKs until after the breakdown of the nuclear envelope during mitosis, when Cdc2 is the CDK that is most active [19].

Associations of PRDX1 with chemical compounds

• Characterization of a mammalian peroxiredoxin that contains one conserved cysteine [20].
• Prx II was reduced by hCyP-A without help from any other reductant, and the reduction was cyclosporin A-independent [15].
• All Prx enzymes contain a conserved Cys residue that undergoes a cycle of peroxide-dependent oxidation and thiol-dependent reduction during catalysis [21].
• Treatment of lung explants with actinomycin D inhibited Prx mRNA increases in 95% oxygen, indicating transcriptional regulation [2].
• In lung explant cultures, specific PKC inhibitors calphostin C or GF109203X inhibited the increase in Prx I mRNA with 95% oxygen exposure, indicating PKC-mediated signaling [2].

Physical interactions of PRDX1

• Thioredoxin reduces exposed protein disulfides and couples with peroxiredoxin to scavenge reactive oxygen species [22].

Enzymatic interactions of PRDX1

• To investigate the catalytic mechanism of the Grx-dependent reduction of hydroperoxides catalyzed by Prx, a series of cysteinic mutants was constructed [23].
• Tryparedoxin, a thioredoxin-related protein from Crithidia fasciculata with a molecular mass of 16 kDa catalyses the reduction of a peroxiredoxin-type peroxidase, Cf21, at the expense of trypanothione [Nogoceke, E., Gommel, D. U., Kiess, M., Kalisz, H. M. & Flohé, L. E. (1997) Biol. Chem. Hoppe-Seyler 378, 827-836] [24].

Regulatory relationships of PRDX1

• Elucidation of ATP-stimulated stress protein expression of RBA-2 type-2 astrocytes: ATP potentiate HSP60 and Cu/Zn SOD expression and stimulates pI shift of peroxiredoxin II [25].
• Peroxiredoxin II functions as a signal terminator for H2O2-activated phospholipase D1 [26].

Other interactions of PRDX1

• Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family [27].
• 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 [1].
• Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 A resolution [28].
• 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) [29].
• PRDX4 is one of six peroxiredoxin-family genes that are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed [17].
• These findings are consistent with the hypothesis that human Prx1 and Prx2 possess unique functions and regulatory mechanisms and that Cys(83) bestows a distinctive identity to Prx1 [30].

Analytical, diagnostic and therapeutic context of PRDX1

• The DNA microarray data for PRDX1 and PRDX3 were reproduced by reverse transcription-PCR analysis [31].
• Two genes, NKEF-A and -B, encode NKEF proteins and sequence analysis presented suggests that each belongs to a highly conserved family of antioxidants [32].
• PRDX I and VI expression did not correlate with disease-free survival in patients with bladder cancer [33].
• Using fluorescence in situ hybridization, the PAG gene was mapped to human chromosome band 1p34 [4].
• Immunohistochemistry of placental tissues showed that the levels of peroxiredoxin III/SP-22 protein were increased in the trophoblasts of floating villi, stromal cells of stem villi, and decidual cells in pre-eclamptic placentae [34].

References