[Prdx1 regulates macrophage polarization by maintaining mitochondrial homeostasis].

In order to investigate the role of Prdx1 in macrophage polarization, mouse leukemia cells of monocyte macrophage (RAW264.7) were treated with lipopolysaccharides (LPS)+ interferon gamma (IFNγ) or IL-4 to induce type 1 macrophage (M1) and type 1 macrophage (M2) macrophages, respectively. The Prdx1 gene knockout cells (Prdx1-/-) were used for the study. Flow cytometry was conducted to detect M1/M2 macrophage markers, and ELISA kits were used to measure M1/M2 cytokine levels. Inducible nitric-oxide synthase (iNOS) activity, arginase-1 (Arg-1) activity, and oxidative damage were also assessed. The Seahorse XFe24 Extracellular Flux Analyzer was employed to measure extracellular acidification rate and oxygen consumption rate. The mitochondrial membrane potential was analyzed using the mitochondrial membrane potential dye (JC-1) fluorescent probe, and mitochondrial superoxide was detected through fluorescence staining. Additionally, the impact of adding a mitochondrial reactive oxygen species (ROS) scavenger on RAW264.7 macrophage polarization was examined. The results demonstrated an increase in ROS, hydrogen peroxide, and 8-hydroxy-2 deoxyguanosine (8-OHDG). Cytotoxicity and mitochondrial toxic effects, including mitochondrial superoxide accumulation, decreased adenosine-triphosphate (ATP) production, reduced mitochondrial membrane potential, and decreased mitochondrial DNA copy number, were observed. Furthermore, down-regulation of translocase of inner mitochondrial membrane 23 (TIM23) mitochondrial protein and mitochondrial stress protein heat shock protein 60 (HSP60) was noted. The extra cellular acidification rate (ECAR) in M1 macrophage polarization in RAW264.7 cells was increased, while oxygen consumption rate (OCR) in M2 macrophages was reduced. These findings indicate that Prdx1 knockout in RAW264.7 cells can inhibit M2 macrophage polarization but promote M1 macrophage polarization by impairing mitochondrial function and reducing oxidative phosphorylation.

SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11- MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

Inactivation of Three Stacked Genes of Cytosolic Peroxiredoxins by Genome Editing.

A set of peroxidases detoxifies H2O2 and mediates H2O2-dependent signal propagation. The peroxidases include peroxiredoxins, glutathione peroxidases, ascorbate peroxidases, and catalases. This at least partial redundancy impedes addressing individual proteins in living plant cells so that the protein functions are often studied by biochemical assays in vitro. In vivo analysis frequently relies on transgenic insertion lines resulting in the knockdown or knockout of the protein of interest. However, many proteins have multiple isoforms in close genomic arrangement so that even crossing of transgenic lines does not allow for a knockdown of all isoforms. The genes encoding for the three cytosolic peroxiredoxins PRXIIB, C, and D in Arabidopsis thaliana are located in close vicinity on chromosome 1 so that crossing over between the genes most rarely occurs and successful crossing of the plants appears impossible. Genome editing instead allows targeting of multiple isoforms and knocks out several genes at once. This chapter describes how to inactivate the three cytosolic peroxiredoxins by CRISPR/Cas9 in A. thaliana.

Molecular characterization, cytoprotective, DNA protective, and immunological assessment of peroxiredoxin-1 (Prdx1) from yellowtail clownfish (Amphiprion clarkii).

Peroxiredoxin-1 (Prdx1) is a thiol-specific antioxidant enzyme that detoxifies reactive oxygen species (ROS) and regulates the redox status of cells. In this study, the Prdx1 cDNA sequence was isolated from the pre-established Amphiprion clarkii (A. clarkii) (AcPrdx1) transcriptome database and characterized structurally and functionally. The AcPrdx1 coding sequence comprises 597 bp and encodes 198 amino acids with a molecular weight of 22.1 kDa and a predicted theoretical isoelectric point of 6.3. AcPrdx1 is localized and functionally available in the cytoplasm and nucleus of cells. The TXN domain of AcPrdx1 comprises two peroxiredoxin signature VCP motifs, which contain catalytic peroxidatic (Cp-C52) and resolving cysteine (CR-C173) residues. The constructed phylogenetic tree and sequence alignment revealed that AcPrdx1 is evolutionarily conserved, and its most closely related counterpart is Amphiprion ocellaris. Under normal physiological conditions, AcPrdx1 was ubiquitously detected in all tissues examined, with the most robust expression in the spleen. Furthermore, AcPrdx1 transcripts were significantly upregulated in the spleen, head kidney, and blood after immune stimulation by polyinosinic:polycytidylic acid (poly (I:C)), lipopolysaccharide (LPS), and Vibrio harveyi injection. Recombinant AcPrdx1 (rAcPrdx1) demonstrated antioxidant and DNA protective properties in a concentration-dependent manner, as evidenced by insulin disulfide reduction, peroxidase activity, and metal-catalyzed oxidation (MCO) assays, whereas cells transfected with pcDNA3.1(+)/AcPrdx1 showed significant cytoprotective function under oxidative and nitrosative stress. Overexpression of AcPrdx1 in fathead minnow (FHM) cells led to a lower viral copy number following viral hemorrhagic septicemia virus (VHSV) infection, along with upregulation of several antiviral genes. Collectively, this study provides insights into the function of AcPrdx1 in defense against oxidative stressors and its role in the immune response against pathogenic infections in A. clarkii.

Specificity and dynamics of H2O2 detoxification by the cytosolic redox regulatory network as revealed by in vitro reconstitution.

The thiol redox state is a decisive functional characteristic of proteins in cell biology. Plasmatic cell compartments maintain a thiol-based redox regulatory network linked to the glutathione/glutathione disulfide couple (GSH/GSSG) and the NAD(P)H system. The basic network constituents are known and in vivo cell imaging with gene-encoded probes have revealed insight into the dynamics of the [GSH]2/[GSSG] redox potential, cellular H2O2 and NAD(P)H+H+ amounts in dependence on metabolic and environmental cues. Less understood is the contribution and interaction of the network components, also because of compensatory reactions in genetic approaches. Reconstituting the cytosolic network of Arabidopsis thaliana in vitro from fifteen recombinant proteins at in vivo concentrations, namely glutathione peroxidase-like (GPXL), peroxiredoxins (PRX), glutaredoxins (GRX), thioredoxins, NADPH-dependent thioredoxin reductase A and glutathione reductase and applying Grx1-roGFP2 or roGFP2-Orp1 as dynamic sensors, allowed for monitoring the response to a single H2O2 pulse. The major change in thiol oxidation as quantified by mass spectrometry-based proteomics occurred in relevant peptides of GPXL, and to a lesser extent of PRX, while other Cys-containing peptides only showed small changes in their redox state and protection. Titration of ascorbate peroxidase (APX) into the system together with dehydroascorbate reductase lowered the oxidation of the fluorescent sensors in the network but was unable to suppress it. The results demonstrate the power of the network to detoxify H2O2, the partially independent branches of electron flow with significance for specific cell signaling and the importance of APX to modulate the signaling without suppressing it and shifting the burden to glutathione oxidation.

Temporal coordination of the transcription factor response to H2O2 stress.

Oxidative stress from excess H2O2 activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H2O2, it is unclear whether they are activated at the same H2O2 concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H2O2 activate p53, NRF2 and JUN. Yet under high H2O2, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H2O2 is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.

Molecular characterization, immune functions and DNA protective effects of peroxiredoxin-1 gene in Antheraea pernyi.

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H2O2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H2O2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H2O2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H2O2 in ApPrx-1-depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects.

Exploring the role of Prx II in mitigating endoplasmic reticulum stress and mitochondrial dysfunction in neurodegeneration.

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.

Restricted glycolysis is a primary cause of the reduced growth rate of zinc-deficient yeast cells.

Zinc is required for many critical processes, including intermediary metabolism. In Saccharomyces cerevisiae, the Zap1 activator regulates the transcription of ∼80 genes in response to Zn supply. Some Zap1-regulated genes are Zn transporters that maintain Zn homeostasis, while others mediate adaptive responses that enhance fitness. One adaptive response gene encodes the 2-cysteine peroxiredoxin Tsa1, which is critical to Zn-deficient (ZnD) growth. Depending on its redox state, Tsa1 can function as a peroxidase, a protein chaperone, or a regulatory redox sensor. In a screen for possible Tsa1 regulatory targets, we identified a mutation (cdc19S492A) that partially suppressed the tsa1Δ growth defect. The cdc19S492A mutation reduced activity of its protein product, pyruvate kinase isozyme 1 (Pyk1), implicating Tsa1 in adapting glycolysis to ZnD conditions. Glycolysis requires activity of the Zn-dependent enzyme fructose-bisphosphate aldolase 1, which was substantially decreased in ZnD cells. We hypothesized that in ZnD tsa1Δ cells, the loss of a compensatory Tsa1 regulatory function causes depletion of glycolytic intermediates and restricts dependent amino acid synthesis pathways, and that the decreased activity of Pyk1S492A counteracted this depletion by slowing the irreversible conversion of phosphoenolpyruvate to pyruvate. In support of this model, supplementing ZnD tsa1Δ cells with aromatic amino acids improved their growth. Phosphoenolpyruvate supplementation, in contrast, had a much greater effect on growth rate of WT and tsa1Δ ZnD cells, indicating that inefficient glycolysis is a major factor limiting yeast growth. Surprisingly however, this restriction was not primarily due to low fructose-bisphosphate aldolase 1 activity, but instead occurs earlier in glycolysis.

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

DDAH1 recruits peroxiredoxin 1 and sulfiredoxin 1 to preserve its activity and regulate intracellular redox homeostasis.

Growing evidence suggests that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a crucial enzyme for the degradation of asymmetric dimethylarginine (ADMA), is closely related to oxidative stress during the development of multiple diseases. However, the underlying mechanism by which DDAH1 regulates the intracellular redox state remains unclear. In the present study, DDAH1 was shown to interact with peroxiredoxin 1 (PRDX1) and sulfiredoxin 1 (SRXN1), and these interactions could be enhanced by oxidative stress. In HepG2 cells, H2O2-induced downregulation of DDAH1 and accumulation of ADMA were attenuated by overexpression of PRDX1 or SRXN1 but exacerbated by knockdown of PRDX1 or SRXN1. On the other hand, DDAH1 also maintained the expression of PRDX1 and SRXN1 in H2O2-treated cells. Furthermore, global knockout of Ddah1 (Ddah1-/-) or liver-specific knockout of Ddah1 (Ddah1HKO) exacerbated, while overexpression of DDAH1 alleviated liver dysfunction, hepatic oxidative stress and downregulation of PRDX1 and SRXN1 in CCl4-treated mice. Overexpression of liver PRDX1 improved liver function, attenuated hepatic oxidative stress and DDAH1 downregulation, and diminished the differences between wild type and Ddah1-/- mice after CCl4 treatment. Collectively, our results suggest that the regulatory effect of DDAH1 on cellular redox homeostasis under stress conditions is due, at least in part, to the interaction with PRDX1 and SRXN1.

Grass carp peroxiredoxin 5 and 6-mediated autophagy inhibit grass carp reovirus replication and mitigate oxidative stress.

Peroxiredoxins (Prxs) are a family of antioxidant enzymes crucial for shielding cells against oxidative damage from reactive oxygen species (ROS). In this study, we cloned and analyzed two grass carp peroxiredoxin genes, CiPrx5 and CiPrx6. These genes exhibited ubiquitous expression across all sampled tissues, with their expression levels significantly modulated upon exposure to grass carp reovirus (GCRV). CiPrx5 was localized in the mitochondria, while CiPrx6 was uniformly distributed in the whole cells. Transfection or transformation of CiPrx5 and CiPrx6 into fish cells or E. coli significantly enhanced host resistance to H2O2 and heavy metals, leading to increased cell viability and reduced cell apoptosis rates. Furthermore, purified recombinant CiPrx5 and CiPrx6 proteins effectively protected DNA against oxidative damage. Notably, overexpression of both peroxiredoxins in fish cells effectively inhibited GCRV replication, reduced intracellular ROS levels induced by GCRV infection and H2O2 treatment, and induced autophagy. Significantly, these functions of CiPrx5 and CiPrx6 in GCRV replication and ROS mitigation were abolished upon treatment with an autophagy inhibitor. In summation, our findings suggest that grass carp Prx5 and Prx6 promote autophagy to inhibit GCRV replication, decrease intracellular ROS, and provide protection against oxidative stress.

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer.

BACKGROUND: Cisplatin (CDDP)-based chemotherapy has emerged as the primary treatment for muscle-invasive bladder cancer and metastatic bladder cancer. Nevertheless, a significant proportion of patients experience rapidly developed chemoresistance, leading to treatment ineffectiveness. Existing evidence suggests that chemoresistance is governed by various factors, including tumor stem cells, epithelial mesenchymal transition, and reactive oxygen species (ROS). However, limited research has been conducted on the role of PRDX2, a crucial ROS scavenger, in the modulation of chemoresistance in bladder cancer. METHODS: Cisplatin-resistant cell lines were established using the concentration gradient overlay method, and differentially expressed genes in resistant cells were screened through RNA sequencing. The expression of PRDX2 in cells and tissues was assessed using RT-qPCR, Western Blot, and immunohistochemistry. The expression of PRDX2 in bladder cancer and adjacent tissues was evaluated using a bladder cancer tissue microarray. Furthermore, the impact of PRDX2 knockdown on tumor formation and metastasis was investigated in vivo by applying subcutaneous tumor xenografts tail vein metastasis assays. RESULTS: We demonstrated that PRDX2 is significantly upregulated in bladder tumors and cisplatin-resistant bladder tumor cell lines. Overexpression of PRDX2 can promote tumor proliferation, migration, and invasion both in vitro and in vivo. We have found that knockdown of PRDX2 expression can effectively reverse cell resistance to cisplatin. Mechanistically, our findings suggest that PRDX2 is involved in regulating tumor stemness and epithelial-mesenchymal transition (EMT). Knockdown of PRDX2 affects the PI3K-AKT and mTOR signaling pathways, thereby influencing tumor stemness and EMT, ultimately impacting the chemotherapy resistance of the tumor. CONCLUSIONS: This study provides a new insight into the regulation of chemotherapy resistance in bladder cancer by PRDX2. Targeting PRDX2 can serve as a potent therapeutic target for chemotherapy resistance.

Triptolide induces apoptosis and cytoprotective autophagy by ROS accumulation via directly targeting peroxiredoxin 2 in gastric cancer cells.

Triptolide, a natural bioactive compound derived from herbal medicine Tripterygium wilfordii, has multiple biological activities including anti-cancer effect, which is being tested in clinical trials for treating cancers. However, the exact mechanism by which Triptolide exerts its cytotoxic effects, particularly its specific protein targets, remains unclear. Here, we show that Triptolide effectively induces cytotoxicity in gastric cancer cells by increasing reactive oxygen species (ROS) levels. Further investigations reveal that ROS accumulation contributes to the induction of Endoplasmic Reticulum (ER) stress, and subsequently autophagy induction in response to Triptolide. Meanwhile, this autophagy is cytoprotective. Interestingly, through activity-based protein profiling (ABPP) approach, we identify peroxiredoxins-2 (PRDX2), a component of the key enzyme systems that act in the defense against oxidative stress and protect cells against hydroperoxides, as direct binding target of Triptolide. By covalently binding to PRDX2 to inhibit its antioxidant activity, Triptolide increases ROS levels. Moreover, overexpression of PRDX2 inhibits and knockdown of the expression of PRDX2 increases Triptolide-induced apoptosis. Collectively, these results indicate PRDX2 as a direct target of Triptolides for inducing apoptosis. Our results not only provide novel insight into the underlying mechanisms of Triptolide-induced cytotoxic effects, but also indicate PRDX2 as a promising potential therapeutic target for developing anti-gastric cancer agents.

Exploring the role of PRDX4 in the development of uterine corpus endometrial carcinoma.

Peroxicedoxin 4 (PRDX4), a member of the peroxicedoxins (PRDXs), has been reported in many cancer-related studies, but its role in uterine corpus endometrial carcinoma (UCEC) is not fully understood. In the present study, we found that PRDX4 was highly expressed in UCEC tissues and cell lines through the combination of bioinformatics analysis and experiments, and elevated PRDX4 levels were associated with poor prognosis. Knockdown of PRDX4 significantly blocked the proliferation and migration of the UCEC cell line Ishikawa and reduced degree of cell confluence. These findings highlight the oncogenic role of PRDX4 in UCEC. In addition, genes that interact with PRDX4 in UCEC were MT-ATP8, PBK, and PDIA6, and we speculated that these genes interacted with each other to promote disease progression in UCEC. Thus, PRDX4 is a potential diagnostic biomarker for UCEC, and targeting PRDX4 may be a potential therapeutic strategy for patients with UCEC.

MiR-92a-2-5p suppresses esophageal squamous cell carcinoma cell proliferation and invasion by targeting PRDX2.

MicroRNAs (miRNAs) can function as negative regulators of gene expression by binding to the 3'-untranslated region (3'-UTR) of target genes. The aberrant expression of miRNAs in neoplasm is extensively associated with tumorigenesis and cancer progression, including esophageal squamous cell carcinoma (ESCC). Our previous investigation has identified the oncogenic roles of Peroxiredoxin2 (PRDX2) in ESCC progression; however, its upstream regulatory mechanism remains to be elucidated. By merging the prediction results from miRWalk2.0 and miRNA differential expression analysis results based on The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) database, eight miRNA candidates were predicted to be the potential regulatory miRNAs of PRDX2, followed by further identification of miR-92a-2-5p as the putative miRNA of PRDX2. Subsequent functional studies demonstrated that miR-92a-2-5p can suppress ESCC cell proliferation and migration, as well as tumor growth in subcutaneous tumor xenograft models, which might be mediated by the suppression of AKT/mTOR and Wnt3a/ß-catenin signaling pathways upon miR-92a-2-5p mimic transfection condition. These data revealed the tumor suppressive functions of miR-92a-2-5p in ESCC by targeting PRDX2.

The effects of Fasciola hepatica recombinant proteins (peroxiredoxin and cathepsin L1) on Crohn's disease experimental model.

The immunomodulatory potential of the excretory-secretory (E/S) proteins of the helminths has been shown in previous investigations. This study evaluated the effects of the recombinants and excretory-secretory proteins of the Fasciola hepatica on induced colitis in Balb/c mice. The F. hepatica Recombinant proteins, Cathepsin L1 and Peroxiredoxin, and E/S proteins were intraperitoneally injected into the three mice groups as the case groups, while the control groups received PBS. Colitis was induced in mice by intraluminal administration of the 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS). After 8 h, the case groups received the second dosage of the treatments, and it was repeated 24 h later. The immunological, pathological, and macroscopic changes were evaluated 3 days after colitis induction. The macroscopic evaluation revealed significantly lower inflammatory scores in the mice treated with recombinant Peroxiredoxin (rPRX) and recombinant Cathepsin L1 (rCL1). Despite the macroscopic observation, the pathological finding was insignificant between the groups. IFN-γ secretion was significantly lower in splenocytes of the groups that received rPRX, rCL1, and E/S than the controls. IL-10 showed significantly higher levels in groups treated with rPRX and rCL1 than controls, whereas the level of IL-4 was not statistically significant. Excretory-secretory proteins of the F. hepatica showed immunomodulatory potency and the main effects observed in this study were through the reduction of inflammatory cytokine and inflammation manifestation as well as induction of anti-inflammatory cytokines.

Dual role of PRDX1 in redox-regulation and tumorigenesis: Past and future.

Tumour cells often display an active metabolic profile, leading to the intracellular accumulation of reactive oxygen species. As a member of the peroxidase family, peroxiredoxin 1 (PRDX1) functions generally in protecting against cell damage caused by H2O2. Additionally, PRDX1 plays a role as a molecular chaperone in various malignant tumours, exhibiting either tumour-promoting or tumour-suppressing effects. Currently, PRDX1-targeting drugs have demonstrated in vitro anticancer effects, indicating the potential of PRDX1 as a molecular target. Here we discussed the diverse functions of PRDX1 in tumour biology and provided a comprehensive analysis of the therapeutic potential of targeting PRDX1 signalling across various types of cancer.

Peroxiredoxin-2 gene in Antheraea pernyi modulates immune functions and protect DNA damage.

Peroxiredoxins have been shown to protect insects from oxidative damage and to play a role in the immune system. In the present study, we cloned and characterized the Antheraea pernyi peroxiredoxin 2 (ApPrx-2) gene, then assessed its functional roles. The ApPrx-2 gene has a 687 bp open reading frame that encodes a protein with 288 amino acid residues. Quantitative real-time PCR analysis revealed that the mRNA levels of ApPrx-2 were highest in the hemocytes. Immune challenge assay revealed that ApPrx-2 transcription could be induced after microbial challenge. A DNA cleavage assay employing recombinant ApPrx-2 protein and a metal-catalyzed oxidation system showed that rApPrx-2 protein could protect supercoiled DNA against oxidative stress. The protein antioxidant activity of rApPrx-2 was examined, and it was found that rApPrx-2 exhibited a high level of antioxidant activity by removing H2O2. In addition, ApPrx-2 knockdown larvae had higher H2O2 levels and a lower survival rate when compared to controls. Interestingly, the antibacterial activity was significantly higher in ApPrx-2 depleted larvae compared with control. Overall, our findings indicate that ApPrx-2 may be involved in a range of physiological functions of A. pernyi, as it protects supercoiled DNA from oxidative stress and regulates antibacterial activity.

Systematic analysis of Prx genes in the Brachypodium genus and their expression pattern under abiotic constraints.

Peroxiredoxins (Prx) are ubiquitous peroxidases required for the removal of excess free radicals produced under stress conditions. Peroxiredoxin genes (Prx) in the Brachypodium genus were identified using bioinformatics tools and their expression profiles were determined under abiotic stress using RT-qPCR. The promoter regions of Prx genes contain several cis-acting elements related to stress response. In silico expression analysis showed that B. distachyon Prx genes (BdPrx) are tissue specific. RT-qPCR analysis revealed their differential expression when exposed to salt or PEG-induced dehydration stress. In addition, the upregulation of BdPrx genes was accompanied by accumulation of H2 O2 . Exogenous application of H2 O2 induced expression of almost all BdPrx genes. The identified molecular interaction network indicated that Prx proteins may contribute to abiotic stress tolerance by regulating key enzymes involved in lignin biosynthesis. Overall, our findings suggest the potential role of Prx genes in abiotic stress tolerance and lay the foundation for future functional analyses aiming to engineer genetically improved cereal lines.