Elimination Of Peroxide Research Articles

Peroxiredoxin as a functional endogenous antioxidant enzyme in pronuclei of mouse zygotes.

Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (H2O2). We here report the cellular localization of hyperoxidized PRDX and its involvement in the antioxidant mechanisms of freshly fertilized oocytes. Treatment of zygotes at the pronuclear stage with H2O2 enhanced pronuclear localization of hyperoxidized PRDX in zygotes and concurrently impaired the generation of 5-hydroxymethylcytosine (5hmC) on the male genome, which is an epigenetic reprogramming event that occurs at the pronuclear stage. Thus, our results suggest that endogenous PRDX is involved in antioxidant mechanisms and epigenetic reprogramming during MZT.

102 - Abnormal Methylation and Redox Homeostasis in the Onset and Progression of Combined Homocystinuria and Methylmalonic Aciduria (MMACHC)

Nutritional and genetic deficiencies of cobalamin (vitamin B12) lead to severe neurological and hematological dysfunction, and in severe cases, to death. Intracellular processing of dietary cobalamins is catalyzed by the glutathione-dependent MMACHC protein, which primes the cobalamin molecule prior to its delivery to cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MM). Dysfunction or absence of MMACHC lead to combined homocystinuria and methylmalonic aciduria (OMIM 609831) by inactivation of MS and MM, respectively. We examined the proteome of cytosolic and nuclear fractions of cultured skin fibroblasts from five healthy neonates and five patients with early onset MMACHC disease. Stable isotope labeling by amino acids in cell culture (SILAC) and mass spectrometry permitted the identification of 3450 proteins. Methylated Arg, Lys and Glu residues were found in 11 histones and 126 non-histone proteins. Significant changes in protein expression levels were confirmed for enzymes of the methionine cycle, the trans-sulfuration pathway, mitochondrial respiration and the elimination of superoxide and peroxides. Targeted metabolomics confirmed functional disturbances in relevant endogenous aminothiols. A direct interaction of MMACHC with heat shock protein 90 was also demonstrated. This is the first study to investigate redox homeostasis in an inherited metabolic disorder without external induction of oxidative stress. Our data suggest that natural mutations in the MMACHC gene impair cellular methylation and redox homeostasis, which may contribute to the vascular and neurological phenotype observed in these patients.

Use of bovine catalase and manganese dioxide for elimination of hydrogen peroxide from partly oxidized aqueous solutions of aromatic molecules – Unexpected complications

Being a toxic substance, hydrogen peroxide (H2O2) formed during application of advanced oxidation processes disturbs the biological assessment of the treated solutions. Therefore, its removal is necessary when the concentration exceeds the critical level relevant to the biological tests. In this study, H2O2 removal was tested using catalase enzyme or MnO2 as catalysts and the concentration changes were measured by the Cu(II)/phenanthroline method. MnO2 and Cu(II) were found to react not only with H2O2 but also with the partly oxidized intermediates formed in the hydroxyl radical induced degradation of aromatic antibiotic and pesticide compounds. Catalase proved to be a milder oxidant, it did not show significant effects on the composition of organic molecules. The Cu(II)/phenanthroline method gives the correct H2O2 concentration only in the absence of easily oxidizable compounds, e.g. certain phenol type molecules.

Expression and Enzyme Activity of Catalase in Chilo suppressalis (Lepidoptera: Crambidae) Is Responsive to Environmental Stresses.

Catalase (CAT) is an important antioxidant enzyme that protects organisms against oxidative stresses by eliminating hydrogen peroxide. In this study, we cloned and characterized a full-length cDNA of CAT from Chilo suppressalis (CsCAT) and examined the influence of environmental stresses on CsCAT expression and enzyme activity. The cDNA contains a 1659-bp open reading frame encoding a polypeptide of 553 amino acids most closely related (90.14%) to Papilio polytes catalases. The CsCAT was expressed in all developmental stages with the highest expression in the fat body, and the CsCAT enzyme activity closely mirrored its observed mRNA expression patterns. The CsCAT mRNA was up-regulated when the larvae were exposed to high temperature (≥30 °C), insecticides (abamectin and chlorantraniliprole), chemicals (H2O2, CHP, CdCl2, and CuSO4), and a dead-end trap plant (vetiver grass), and the CsCAT enzyme activity again mirrored the observed CsCAT expression patterns. These results suggest that up-regulation of CsCAT may enhance the defense response of C. suppressalis by weakening the effects of environmental stresses, and provide insight into the role of CsCAT during development of C. suppressalis.

Control of Electrons' Spin Eliminates Hydrogen Peroxide Formation During Water Splitting.

The production of hydrogen through water splitting in a photoelectrochemical cell suffers from an overpotential that limits the efficiencies. In addition, hydrogen-peroxide formation is identified as a competing process affecting the oxidative stability of photoelectrodes. We impose spin-selectivity by coating the anode with chiral organic semiconductors from helically aggregated dyes as sensitizers; Zn-porphyrins and triarylamines. Hydrogen peroxide formation is dramatically suppressed, while the overall current through the cell, correlating with the water splitting process, is enhanced. Evidence for a strong spin-selection in the chiral semiconductors is presented by magnetic conducting (mc-)AFM measurements, in which chiral and achiral Zn-porphyrins are compared. These findings contribute to our understanding of the underlying mechanism of spin selectivity in multiple electron-transfer reactions and pave the way toward better chiral dye-sensitized photoelectrochemical cells.

Functional analysis of a novel hydrogen peroxide resistance gene in Lactobacillus casei strain Shirota.

Lactic acid bacteria have a variety of mechanisms for tolerance to oxygen and reactive oxygen species, and these mechanisms differ among species. Lactobacillus casei strain Shirota grows well under aerobic conditions, indicating that the various systems involved in oxidative stress resistance function in this strain. To elucidate the mechanism of oxidative stress resistance in L. casei strain Shirota, we examined the transcriptome response to oxygen or hydrogen peroxide exposure. We then focused on an uncharacterized gene that was found to be up-regulated by both oxygen and hydrogen peroxide stress; we named the gene hprA1 (hydrogen peroxide resistance gene). This gene is widely distributed among lactobacilli. We investigated the involvement of this gene in oxidative stress resistance, as well as the mechanism of tolerance to hydrogen peroxide. Growth of L. casei MS105, an hprA1-disrupted mutant, was not affected by oxygen stress, whereas the survival rate of MS105 after hydrogen peroxide treatment was markedly reduced compared to that of the wild-type. However, the activity of MS105 in eliminating hydrogen peroxide was similar to that of the wild-type. We cloned hprA1 from L. caseiShirota and purified recombinant HprA1 protein from Escherichia coli. We demonstrated that the recombinant HprA1 protein bound to iron and prevented the formation of a hydroxyl radical in vitro. Thus, HprA1 protein probably contributes to hydrogen peroxide tolerance in L. casei strain Shirota by binding to iron in the cells and preventing the formation of a hydroxyl radical.

Stress hardening under long-term cadmium treatment is correlated with the activation of antioxidative defence and iron acquisition of chloroplasts in Populus.

Cadmium (Cd), a highly toxic heavy metal affects growth and metabolic pathways in plants, including photosynthesis. Though Cd is a transition metal with no redox capacity, it generates reactive oxygen species (ROS) indirectly and causes oxidative stress. Nevertheless, the mechanisms involved in long-term Cd tolerance of poplar, candidate for Cd phytoremediation, are not well known. Hydroponically cultured poplar (Populus jacquemontiana var. glauca cv. 'Kopeczkii') plants were treated with 10 μM Cd for 4 weeks. Following a period of functional decline, the plants performed acclimation to the Cd induced oxidative stress as indicated by the decreased leaf malondialdehyde (MDA) content and the recovery of most photosynthetic parameters. The increased activity of peroxidases (PODs) could have a great impact on the elimination of hydrogen peroxide, and thus the recovery of photosynthesis, while the function of superoxide dismutase (SOD) isoforms seemed to be less important. Re-distribution of the iron content of leaf mesophyll cells into the chloroplasts contributed to the biosynthesis of the photosynthetic apparatus and some antioxidative enzymes. The delayed increase in photosynthetic activity in relation to the decline in the level of lipid peroxidation indicates that elimination of oxidative stress damage by acclimation mechanisms is required for the restoration of the photosynthetic apparatus during long-term Cd treatment.

Molecular cloning, characterization and expression analysis of a catalase gene in Paphia textile

Catalase is an important antioxidant protein that can protect organisms against various forms of oxidative damage by eliminating hydrogen peroxide. In this study, the catalase cDNA of Paphia textile (PtCAT) was cloned using RTPCR and rapid amplification of cDNA ends (RACE). PtCAT is 1 921 bp long and consists of a 5′-UTR of 50 bp, a 3′-UTR of 349 bp, and an ORF of 1 542 bp that encodes 513 amino acids with a molecular weight of 58.4 kD and an estimated isoelectric point of 8.2. Sequence alignment indicated that PtCAT contained a highly conserved catalytic signature motif (61FNRERIPERVVHAKGAG77), a proximal heme-ligand signature sequence (352RLFSYSDP359), and three catalytic amino acid residues (H72, N145, and Y356). PtCAT also contains two putative N-glycosylation sites (34NKT36 and 437NFT439) and a peroxisome-targeting signal (511AQL513). Furthermore, PtCAT shares 53%–88% identity and 29%–89% similarity with other catalase amino acid sequences. PtCAT mRNA was present in all tested organs, including the heart, digestive gland, adductor muscle, gonad, gill, and mantle, but its expression was highest in the digestive gland. High-temperature-induced stress produced two expression patterns of PtCAT mRNA: first, an initial up-regulation followed by a down-regulation in the heart, digestive gland, and gonad and, second, consistent down-regulation in all other organs. These results demonstrate that PtCAT is a typical member of the catalase family and might be involved in the responses to harmful environmental factors.

Effective Killing of Cancer Cells Through ROS-Mediated Mechanisms by AMRI-59 Targeting Peroxiredoxin I.

The intrinsic increase of reactive oxygen species (ROS) production in cancer cells after malignant transformation frequently induces redox adaptation, leading to enhanced antioxidant capacity. Peroxiredoxin I (PrxI), an enzyme responsible for eliminating hydrogen peroxide, has been found to be elevated in many types of cancer cells. Since overexpression of PrxI promoted cancer cells' survival and resistance to chemotherapy and radiotherapy, PrxI has been proposed as a therapeutic target for anticancer drugs. In this study, we aimed to investigate the anticancer efficacy of a small molecule inhibitor of PrxI. By a high-throughput screening approach, we identified AMRI-59 as a potent inhibitor of PrxI. AMRI-59 increased cellular ROS, leading to the activation of both mitochondria- and apoptosis signal-regulated kinase-1-mediated signaling pathways, resulting in apoptosis of A549 human lung adenocarcinoma. AMRI-59 caused no significant changes in ROS level, proliferation, and apoptosis of PrxI-knockdown A549 cells by RNA interference. PrxI overexpression or N-acetylcysteine pretreatment abrogated AMRI-59-induced cytotoxicity in A549 cells. AMRI-59 rendered tumorigenic ovarian cells more susceptible to ROS-mediated death compared with nontumorigenic cells. Moreover, significant antitumor activity of AMRI-59 was observed in mouse tumor xenograft model implanted with A549 cells with no apparent acute toxicity. This study offers preclinical proof-of-concept for AMRI-59, a lead small molecule inhibitor of PrxI, as an anticancer agent. Our results highlight a promising strategy for cancer therapy that preferentially eradicates cancer cells by targeting the PrxI-mediated redox-dependent survival pathways.

Immobilizing Systems Biocatalysis for the Selective Oxidation of Glycerol Coupled to In Situ Cofactor Recycling and Hydrogen Peroxide Elimination

AbstractThe front cover artwork for Issue 13/2015 is provided by the groups of Prof. Jose M. Guisan, Instituto de Catálisis y Petroleoquímica (Spain) and Dr. Fernando López‐Gallego, CIC BiomaGUNE and Basque Foundation for Science (Spain). The image shows a co‐immobilized trienzyme system catalyzing a one‐pot cascade reaction to oxidize glycerol from the biodiesel industry to dihydroxyacetone, which is a valuable chemical for industry. See the Full Paper itself at http://dx.doi.org/10.1002/cctc.201500210.

Cover Picture: Immobilizing Systems Biocatalysis for the Selective Oxidation of Glycerol Coupled to In Situ Cofactor Recycling and Hydrogen Peroxide Elimination (ChemCatChem 13/2015)

Cover Picture: Immobilizing Systems Biocatalysis for the Selective Oxidation of Glycerol Coupled to In Situ Cofactor Recycling and Hydrogen Peroxide Elimination (ChemCatChem 13/2015)

CDNA cloning, characterization and expression analysis of manganese superoxide dismutase in Ulva prolifera

Superoxide dismutase (SOD) is an important antioxidant protein that protects organisms against various oxidative stresses by eliminating hydrogen peroxide. In the present study, a full-length cDNA sequence of manganese superoxide dismutase (MnSOD) from the Ulva prolifera (denoted as UpMnSOD) was cloned by a reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end method. The UpMnSOD cDNA sequence contained 955 bp with an open reading frame of 699 bp encoding 232 amino acid residues. The cDNA contained a 5′-untranslated region (UTR) of 29 bp nucleotides and a long 3′-UTR of 227 bp nucleotides. The calculated molecular mass was 25.7 kDa, and the estimated isoelectronic point (pI) of this protein was 6.83. Histidine (His) 59, His103, His194, and aspartate (Asp) 190 were found to be activated sites in UpMnSOD. Multiple alignment analysis revealed that the deduced amino acid sequence of MnSOD shared high identity (86 %) with Ulva fasciata. A phylogenetic tree construct indicated that UpMnSOD clustered into one subgroup with the MnSOD from U. fasciata. Quantitative real-time analysis revealed that UpMnSOD expression was induced at both 35 and 5 °C. The result indicated that UpMnSOD expression levels reached a maximum point of 2.63-fold (P < 0.05) and 1.28-fold compared to the control at 25 °C after 6-h treatment at 35 and 5 °C, respectively, and that long-time heat shock and cold treatment decreased the mRNA expression levels of MnSOD. Furthermore, UpMnSOD expression increased after 15 °C treatment, a 2.4-fold increase after 12-h treatment. Treatment with 1 mmol·L−1 salicylic acid (SA) at 35 °C also increased the gene expression of UpMnSOD and reached a maximum of 1.48-fold of the control after 6-h treatment, followed by a gradual decrease. However, the gene expression level of UpMnSOD increased rapidly within 3 h then decreased quickly under SA 5 mmol·L−1 + 35 °C. These data indicate that MnSOD was perhaps involved in the acute response against temperature stress, and salicylic acid could alleviate the high temperature stress effect on U. prolifera.

Immobilizing Systems Biocatalysis for the Selective Oxidation of Glycerol Coupled to In Situ Cofactor Recycling and Hydrogen Peroxide Elimination

AbstractThe combination of three different enzymes immobilized rationally on the same heterofunctional carrier allowed the selective oxidation of glycerol to 1,3‐dihydroxyacetone (DHA) coupled to in situ redox‐cofactor recycling and H2O2 elimination. In this cascade, engineered glycerol dehydrogenase with reduced product inhibition oxidized glycerol selectively to DHA with the concomitant reduction of NAD+ to NADH. NADH oxidase regenerated the NAD+ pool by oxidizing NADH to NAD+ to form H2O2 as the byproduct. Finally, catalase eliminated H2O2 to yield water and O2 as innocuous products, which avoided the spontaneous DHA oxidation triggered by H2O2. The co‐immobilization of the three enzymes on the same porous carrier allowed the in situ recycling and disproportionation of the redox cofactor and H2O2, respectively, to produce up to 9.5 mM DHA, which is 18‐ and 6‐fold higher than glycerol dehydrogenase itself and a soluble multienzyme system, respectively.

Interaction of ROS and RNS with GSH and GSH/GPX Systems

Rapid reactivity amongst the free radicals and its capability to inflict severe damages to cell has evolved cell redox systems with multiple pathways of counteracting and counterbalancing mechanisms. One of the important cell redox pathways is glutathione (GSH) and GSH/glutathione peroxidase (GPX) enzyme system. In addition to eliminating hydrogen peroxide (H2O2) and peroxynitrite (ONOO‐), GSH and GPX act as a buffer to protect crucial proteins against pathological modifications. In recent year, GSH and GPX have been emphasized for providing a promising treatment avenue in vascular diseases including neurovascular and cardiovascular diseases. However, complexity of cellular redox system has limited the current understanding of GSH and GPX led mechanism which prevents cell damage in pathophysiological condition. In this study, we used systems approach to model GSH and the GSH/GPX system in the presence of nitric oxide (NO) and superoxide (O2•‐) derived species. Result shows that there is an indicated dividing line between oxidative stress and nitrosative stress as the ratio of [O2•‐]/[NO] less than or greater than one. Results provide quantitative information about GSH levels that leads to the depletion of N2O3 and H2O2. In addition, reduced glutathione peroxidase (GPXr) assists GSH in removal of high levels of H2O2. The model predicted that the GPX antioxidant capabilities are dependent on the bioavailability of GSH. The levels of nitric oxide and superoxide derived species are dependent of the balance between these reactive and antioxidant species through interaction with GSH/GPX system. The results indicate that both GSH and GPX play an important role in removal of oxidative stress and GSH also plays an important role in detoxifying nitrosative stress.

Growth inhibition and altered gene transcript levels in earthworms (Eisenia fetida) exposed to 2,2',4,4'-tetrabromodiphenyl ether.

The toxic effects of the ubiquitous pollutant 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on the earthworm Eisenia fetida were assessed by determining growth-inhibition and gene transcript levels of superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), and transcriptional changes of the stress-response gene (heat-shock protein 70 [Hsp70]). Somatic growth and growth-inhibition rates in all BDE-47-treated groups were significantly different from those of the controls. The SOD gene transcripts were upregulated at all exposure doses and reached the maximum at the concentration of 400 mg/kg dry weight (dw) (3.84-fold, P < 0.01), which protected earthworms from oxidative stresses. However, downregulation of CAT and Hsp70 was present in all exposure doses and reached to the minimum at concentrations of 400 mg/kg dw (0.07-fold, P < 0.01 and 0.06-fold, P < 0.01, respectively). Upregulation of GST gene transcript level presented significant changes at concentrations of 10 (2.69-fold, P < 0.05) and 100 mg/kg dw (2.55-fold, P < 0.05). SOD maintained a dynamic balance to upregulate SOD expression to eliminate superoxide radicals in all dosage treatments, but downregulation of CAT decreased the ability to eliminate hydrogen peroxide. These changes could result in biochemical and physiological disturbances in earthworms.

Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity

ObjectiveInflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it...

The biological importance of glutathione peroxidase and peroxiredoxin backup systems in bivalves during peroxide exposure

Organic peroxide elimination in eukaryotes essentially depends on glutathione peroxidase (GPx) and peroxiredoxin (Prx) enzymes, which are supported by their respective electron donors, glutathione (GSH) and thioredoxin (Trx). This system depends on the ancillary enzymes glutathione reductase (GR) and thioredoxin reductase (TrxR) to maintain GSH and Trx in their reduced state. This study discusses the biological importance of GR and TrxR in supporting GPx and Prx during cumene hydroperoxide (CHP) exposure in brown mussel Perna perna. ZnCl2 or 1-chloro-2,4-dinitrobenze (CDNB) was used to decrease GR and TrxR activities in gills, as already reported with mammals and bivalves. ZnCl2 exposure lowered GR activity (28%), impaired the in vivo CHP decomposition and decreased the survival rates under CHP exposure. CDNB decreased GR (54%) and TrxR (73%) activities and induced glutathione depletion (99%), promoting diminished peroxide elimination and survival rates at a greater extent than ZnCl2. CDNB also increased the susceptibility of hemocytes to CHP toxicity. Despite being toxic and causing mortality at longer exposures, short (2 h) exposure to CHP promoted an up regulation of GSH (50 and 100 μM CHP) and protein-thiol (100 μM CHP) levels, which was blocked by ZnCl2 or CDNB pre-exposure. Results highlight the biological importance of GSH, GR and TrxR in supporting GPx and Prx activities, contributing to organic peroxides elimination and mussel survival under oxidative challenges. To our knowledge, this is the first work that demonstrates, albeit indirectly, the biological importance of GPx/GR/GSH and Prx/TrxR/Trx systems on in vivo organic peroxide elimination in bivalves.

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Selenocysteine is inserted into selenoproteins via the translational recoding of a UGA codon, normally used as a stop signal. This process depends on the nature of the selenocysteine insertion sequence element located in the 3' UTR of selenoprotein mRNAs, selenium bioavailability, and, possibly, exogenous stimuli. To further understand the function and regulation of selenoproteins in antioxidant defense and redox homeostasis, we investigated how oxidative stress influences selenoprotein expression as a function of different selenium concentrations. We found that selenium supplementation of the culture media, which resulted in a hierarchical up-regulation of selenoproteins, protected HEK293 cells from reactive oxygen species formation. Furthermore, in response to oxidative stress, we identified a selective up-regulation of several selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2). Interestingly, the response was more efficient when selenium was limiting. Although a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by up-regulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, selenocysteine-specific elongation factor, and L30 recoding factors from the cytoplasm to the nucleus.

C4a-Hydroperoxyflavin Formation in N-Hydroxylating Flavin Monooxygenases Is Mediated by the 2′-OH of the Nicotinamide Ribose of NADP+

Flavin-dependent monooxygenases must stabilize a C4a-hydroperoxyflavin intermediate to hydroxylate their respective substrates. Formation and decay of the C4a-hydroperoxyflavin were monitored under rapid reaction kinetic conditions in SidA, an N-hydroxylating monooxygenase involved in siderophore biosynthesis. Solvent kinetic isotope effect studies of flavin oxidation indicate that both hydrogen peroxide elimination and water elimination occur via abstraction of hydrogen from the N5 of the flavin. Kinetic isotope effect and density functional theory results are consistent with the transfer of a proton from the 2'-OH of the nicotinamide ribose of nicotinamide adenine dinucleotide phosphate (NADP⁺) to the C4a-peroxyflavin to form the C4a-hydroperoxyflavin. This represents a novel role for NADP⁺ in the reaction of flavin-dependent enzymes.

Ablation of Peroxiredoxin II Attenuates Experimental Colitis by Increasing FoxO1-Induced Foxp3+ Regulatory T Cells

Peroxiredoxin (Prx) II is an intracellular antioxidant molecule that eliminates hydrogen peroxide, employing a high substrate-binding affinity. PrxII deficiency increases the levels of intracellular reactive oxygen species in many types of cells, which may increase reactive oxygen species-mediated inflammation. In this study, we investigated the susceptibility of PrxII knockout (KO) mice to experimentally induced colitis and the effects of PrxII on the immune system. Wild-type mice displayed pronounced weight loss, high mortality, and colon shortening after dextran sulfate sodium administration, whereas colonic inflammation was significantly attenuated in PrxII KO mice. Although macrophages were hyperactivated in PrxII KO mice, the amount of IFN-γ and IL-17 produced by CD4(+) T cells was substantially reduced. Foxp3(+) regulatory T (Treg) cells were elevated, and Foxp3 protein expression was increased in the absence of PrxII in vitro and in vivo. Restoration of PrxII into KO cells suppressed the increased Foxp3 expression. Interestingly, endogenous PrxII was inactivated through hyperoxidation during Treg cell development. Furthermore, PrxII deficiency stabilized FoxO1 expression by reducing mouse double minute 2 homolog expression and subsequently activated FoxO1-mediated Foxp3 gene transcription. PrxII overexpression, in contrast, reduced FoxO1 and Foxp3 expression. More interestingly, adoptive transfer of naive CD4(+) T cells from PrxII KO mice into immune-deficient mice attenuated T cell-induced colitis, with a reduction in mouse double minute 2 homolog expression and an increase in FoxO1 and Foxp3 expression. These results suggest that inactivation of PrxII is important for the stability of FoxO1 protein, which subsequently mediates Foxp3(+) Treg cell development, thereby attenuating colonic inflammation.