Peroxidase genes (Prdx) encode a family of antioxidant proteins, which can protect cells from oxidative damage by reducing various cellular peroxides. This study investigated the spatiotemporal expression patterns of gene members in this family during the early development of Xenopus tropicalis. Real-time quantitative PCR showed that all members of this gene family have a distinct temporal expression pattern during the early development of X. tropicalis embryos. Additionally, whole mount in situ hybridization revealed that individual prdx genes display differential expression patterns, with overlapping expression in lymphatic vessels, pronephros, proximal tubule, and branchial arches. This study provides a basis for further study of the function of the prdx gene family.

Obesity is one of the world\'s diseases that endanger human health, causing systemic inflammation caused by excessive reactive oxygen damage. An increase in the proportion of obese people with reduced sperm motility has been reported. But the mechanism behind it remains unclear. Peroxiredoxin 2 (PRDX2) is a member of the peroxidase family that effectively removes hydrogen peroxide. This study is to clarify the expression of PRDX2 in the testes of obese mice and lay a foundation for further exploration of the regulatory and protective effects of PRDX2 on spermatogenesis.
A model of high-fat-induced obesity in animals was constructed, and the expression of PRDX2 in the testes of the two groups was detected by immunohistochemistry, western blotting, immunofluorescence and other techniques. Hydrogen peroxide (H2O2) and cholesterol were co-cultured in testicular support cells for 48 h to observe the expression of PRDX2.
PRDX2 expression was reduced in the testes of the obese group, and immunohistochemistry showed that it was mainly localized to supporting cells. H2O2 inhibits the expression of PRDX2 in Sertoli cells, and high cholesterol upregulates the expression of PRDX2 in Sertoli cells.
PRDX2 has some antioxidant properties against changes in the testicular environment caused by HFD. And under short-term oxidative stress to enhance its antioxidant capacity. PRDX2 may be involved in maintaining the oxidative balance of the spermatogenesis environment.

The peroxidase family of peroxiredoxins (PRDXs) plays a vital role in maintaining the intracellular balance of ROS. However, their function in head and neck squamous cell carcinoma (HNSCC) has not been investigated. We therefore explored the value of PRDXs in HNSCC. We found that the expression of PRDX1, PRDX4, and PRDX5 in HNSCC increased while the expression of PRDX2 decreased. Moreover, the high expression of PRDX4/5/6 indicated a poor prognosis. Lower expression of PRDX1/5 was linked to more immune cell infiltration, higher expression of immune-related molecules and a more likely response to anti-PD-1 treatment. Moreover, PRDX5 knockdown inhibited HNSCC cell proliferation, invasion and metastasis and it might promote apoptosis through its antioxidant property. Taken together, our study highlights the potential role of PRDXs in HNSCC. The function of PRDX5 in the development of HNSCC and the formation of the immune microenvironment makes it a promising potential therapeutic target.

Peroxiredoxins (Prdxs) sense and assess peroxide levels, and signal through protein interactions. Understanding the role of the multiple structural and post-translational modification (PTM) layers that tunes the peroxiredoxin specificities is still a challenge. In this review, we give a tabulated overview on what is known about human and bacterial peroxiredoxins with a focus on structure, PTMs, and protein-protein interactions. Armed with numerous cellular and atomic level experimental techniques, we look at the future and ask ourselves what is still needed to give us a clearer view on the cellular operating power of Prdxs in both stress and non-stress conditions.

BACKGROUND: The peroxiredoxins (PRDXs) gene family has been demonstrated to participate in carcinogenesis and development of numerous cancers and the prognostic values in several cancers have been evaluated already. Purpose of our research is to explore the expression profiles and prognostic values of PRDXs in breast cancer (BrCa).
METHODS: The transcriptional levels of PDRX family members in primary BrCa tissues and their association with intrinsic subclasses were analyzed using UALCAN database. Then, the genetic alterations of PDRXs were examined by cBioPortal database. Moreover, the prognostic values of PRDXs in BrCa patients were investigated via the Kaplan-Meier plotter.
RESULTS: The transcriptional levels of most PRDXs family members in BrCa tissues were significantly elevated compared with normal breast tissues. Meanwhile, dysregulated PRDXs expression was associated with intrinsic subclasses of BrCa. Besides, copy number alterations (CNA) of PRDXs positively regulated their mRNA expressions. Furthermore, high mRNA expression of PRDX4/6 was significantly associated with poor overall survival (OS) in BrCa patients, while high mRNA expression of PRDX3 was notably related to favorable OS. Simultaneously, high mRNA expression of PRDX1/2/4/5/6 was significantly associated with shorter relapse-free survival (RFS) in BrCa patients, while high mRNA expression of PRDX3 was notably related to favorable RFS. In addition, the prognostic value of PRDXs in the different clinicopathological features based on intrinsic subclasses and chemotherapeutic treatment of BrCa patients was further assessed in the KM plotter database.
CONCLUSIONS: Our findings systematically elucidate the expression profiles and distinct prognostic values of PRDXs in BrCa, which might provide novel therapeutic targets and potential prognostic biomarkers for BrCa patients.

Reactive oxygen and nitrogen species have cell signaling properties and are involved in a multitude of processes beyond redox homeostasis. The peroxiredoxin (Prdx) proteins are highly sensitive intracellular peroxidases that can coordinate cell signaling via direct reactive species scavenging or by acting as a redox sensor that enables control of binding partner activity. Oxidation of the peroxidatic cysteine residue of Prdx proteins are the classical post-translational modification that has been recognized to modulate downstream signaling cascades, but increasing evidence supports that dynamic changes to phosphorylation of Prdx proteins is also an important determinant in redox signaling. Phosphorylation of Prdx proteins affects three-dimensional structure and function to coordinate cell proliferation, wound healing, cell fate and lipid signaling. The advent of large proteomic datasets has shown that there are many opportunities to understand further how phosphorylation of Prdx proteins fit into intracellular signaling cascades in normal or malignant cells and that more research is necessary. This review summarizes the Prdx family of proteins and details how post-translational modification by kinases and phosphatases controls intracellular signaling.

UNASSIGNED: The peroxiredoxin (PRDX) protein family is involved in cancer cell invasion and metastasis, but its prognostic value in lung cancer remain elusive.
UNASSIGNED: In this report, we accessed the overall survival (OS) of each individual PRDX mRNA expression through the Kaplan-Meier plotter (KM plotter) database, in which updated gene expression data and survival information include a total of 1,926 lung cancer patients.
UNASSIGNED: Our results indicated that PRDX1 and PRDX2 mRNA expressions were associated with improved OS in all lung cancer patients especially in lung adenocarcinoma patients, whereas PRDX5 and PRDX6 mRNA expressions were associated with poor OS in all lung cancer patients. In addition, the prognostic value of PRDXs in the different clinicopathological features according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of lung cancer patients was further assessed in the KM plotter database by the multivariate cox regression analysis.
UNASSIGNED: Our finding will elucidate the prognostic role of PRDXs in lung cancer and might promote development of PRDX-targeted inhibitors for the treatment of lung cancer.

Alcohol abuse suppresses the immune responses of alveolar macrophages (AMs) and increases the risk of a respiratory infection via chronic oxidative stress and depletion of critical antioxidants within alveolar cells and the alveolar lining fluid. Although alcohol-induced mitochondrial oxidative stress has been demonstrated, the oxidation of the mitochondrial thioredoxin redox circuit in response to alcohol has not been examined. In vitro ethanol exposure of a mouse AM cell line and AMs from ethanol-fed mice demonstrated NADPH depletion concomitant with oxidation of mitochondrial glutathione and oxidation of the thioredoxin redox circuit system including thioredoxin 2 (Trx2) and thioredoxin 2 reductase (Trx2R). Mitochondrial peroxiredoxins (Prdx\'s), which are critical for the reduction of the thioredoxin circuit, were irreversibly hyperoxidized to an inactive form. Ethanol also decreased the mRNAs for Trx2, Trx2R, Prdx3, and Prdx5 plus the mitochondrial thiol-disulfide proteins glutaredoxin 2, glutathione reductase, and glutathione peroxidase 2. Thus, the mitochondrial thioredoxin circuit was highly oxidized by ethanol, thereby compromising the mitochondrial antioxidant capacity and ability to detoxify mitochondrial reactive oxygen species. Oxidation of the mitochondrial thioredoxin redox circuit would further compromise the transient oxidation of thiol groups within specific proteins, the basis of redox signaling, and the processes by which cells respond to oxidants. Impaired mitochondria can then jeopardize cellular function of AMs, such as phagocytosis, which may explain the increased risk of respiratory infection in subjects with an alcohol use disorder.

Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. The aim of this study was to scale-up expression and purification of rhLF in a CHO expression system, verify its glycan primary structure, and assess its biological properties in cell culture models. A stable CHO cell line producing >200mg/L of rhLF was developed and established. rhLF was purified by a single-step cation-exchange chromatography procedure. The highly homogenous rhLF has a molecular weight of approximately 80 kDa. MALDI-TOF mass spectrometric analysis revealed N-linked, partially sialylated glycans at two glycosylation sites, typical for human milk LF. This novel rhLF showed a protective effect against oxidative stress in a similar manner to its natural counterpart. In addition, rhLF revealed a modulatory effect on cellular redox via upregulation of key antioxidant enzymes. These data imply that the CHO-derived rhLF is fully compatible with the native molecule, thus it has promise for human therapeutic applications.

BACKGROUND: The thioredoxin system maintains redox balance through the action of thioredoxin and thioredoxin reductase. Thioredoxin regulates the activity of various substrates, including those that function to counteract cellular oxidative stress. These include the peroxiredoxins, methionine sulfoxide reductase A and specific transcription factors. Of particular relevance is Redox Factor-1, which in turn activates other redox-regulated transcription factors.
METHODS: Experimentally defined transcription factor binding sites in the human thioredoxin and thioredoxin reductase gene promoters together with promoters of the major thioredoxin system substrates involved in regulating cellular redox status are discussed. An in silico approach was used to identify potential putative binding sites for these transcription factors in all of these promoters.
CONCLUSIONS: Our analysis reveals that many redox gene promoters contain the same transcription factor binding sites. Several of these transcription factors are in turn redox regulated. The ARE is present in several of these promoters and is bound by Nrf2 during various oxidative stress stimuli to upregulate gene expression. Other transcription factors also bind to these promoters during the same oxidative stress stimuli, with this redundancy supporting the importance of the antioxidant response. Putative transcription factor sites were identified in silico, which in combination with specific regulatory knowledge for that gene promoter may inform future experiments.
CONCLUSIONS: Redox proteins are involved in many cellular signalling pathways and aberrant expression can lead to disease or other pathological conditions. Therefore understanding how their expression is regulated is relevant for developing therapeutic agents that target these pathways.