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International Journal of Molecular... Apr 2017The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and... (Review)
Review
The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species. The human vanin gene family consists of three genes: , and . All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α.
Topics: Amidohydrolases; Carcinogenesis; Colorectal Neoplasms; Cysteamine; Enzyme Inhibitors; Humans; Inflammation; Peroxidase; Reactive Oxygen Species
PubMed: 28448444
DOI: 10.3390/ijms18050918 -
Frontiers in Immunology 2019Peroxidase enzymes can oxidize a multitude of substrates in diverse biological processes. According to the latest phylogenetic analysis, there are four major heme... (Review)
Review
Peroxidase enzymes can oxidize a multitude of substrates in diverse biological processes. According to the latest phylogenetic analysis, there are four major heme peroxidase superfamilies. In this review, we focus on certain members of the cyclooxygenase-peroxidase superfamily (also labeled as animal heme peroxidases) and their connection to specific NADPH oxidase enzymes which provide HO for the one- and two-electron oxidation of various peroxidase substrates. The family of NADPH oxidases is a group of enzymes dedicated to the production of superoxide and hydrogen peroxide. There is a handful of known and important physiological functions where one of the seven known human NADPH oxidases plays an essential role. In most of these functions NADPH oxidases provide HO for specific heme peroxidases and the concerted action of the two enzymes is indispensable for the accomplishment of the biological function. We discuss human and other metazoan examples of such cooperation between oxidases and peroxidases and analyze the biological importance of their functional interaction. We also review those oxidases and peroxidases where this kind of partnership has not been identified yet.
Topics: Animals; Eosinophils; Hemeproteins; Humans; Hydrogen Peroxide; Leukocytes; NADPH Oxidases; Oxidation-Reduction; Peroxidase; Prostaglandin-Endoperoxide Synthases
PubMed: 30891045
DOI: 10.3389/fimmu.2019.00394 -
Rheumatology (Oxford, England) Sep 2023To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype.
OBJECTIVE
To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype.
METHODS
A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems.
RESULTS
rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619.
CONCLUSIONS
Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
Topics: Female; Humans; Male; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Myeloblastin; Peroxidase; Sex Characteristics
PubMed: 37004177
DOI: 10.1093/rheumatology/kead152 -
BMC Oral Health Jan 2021Disturbances in the levels of serum constituents occurring in chronic renal diseases can be reflected in the saliva composition. The aim of this study was to assess some...
BACKGROUND
Disturbances in the levels of serum constituents occurring in chronic renal diseases can be reflected in the saliva composition. The aim of this study was to assess some selected salivary components in children suffering from idiopathic steroid-sensitive nephrotic syndrome (iNS).
METHODS
A case-control study was performed on iNS and healthy participants. In unstimulated mixed saliva, pH, buffer capacity, total protein, α-amylase, peroxidase, calcium, magnesium, inorganic phosphate, fluoride, urea, uric acid and salivary flow rate were measured. Oral condition was assessed using dmft, DMFT, API and GI indices, usage of fluoride specimens and frequency of tooth brushing. Statistical analysis was performed by Shapiro-Wilk, Brown-Forsythe, Student's t, ANOVA, Tukey's and Pearson's chi-square tests, Pearson's and Spearman's correlations, logistic regression and receiver operating characteristic (ROC) curve analysis.
RESULTS
The study involved 94 participants of both genders aged 4-17 (47 cases in relapse or remission phase of iNS and 47 controls) who were treated in the clinic of pediatric nephrology or outpatient dental clinic. Neither group differed in the number of caries-affected primary and permanent teeth, gingival condition or use of fluoride specimens. The iNS group presented lower levels of magnesium (0.41 ± 0.34 vs. 0.60 ± 0.38 mg/dL, P < 0.05) and fluoride (0.15 ± 0.10 vs. 0.21 ± 0.10 ppm, P < 0.01) and higher contents of urea (35.19 ± 15.55 vs. 25.21 ± 10.78 mg/dL, P < 0.01) and uric acid (2.90 ± 1.23 vs. 2.34 ± 1.04 mg/dL, P < 0.05) than the controls. In the iNS participants with relapse, a higher peroxidase activity and lower magnesium content than in the remission phase were found. ROC analysis showed a weak discriminatory power of these salivary constituents for the differentiation of participants with and without disease (accuracy from 66.0 to 67.0%, area under the ROC curve (AUC) from 0.638 to 0.682) and the relapse and remission phases (accuracy 70.2% and 68.1% and AUC 0.717 and 0.675, respectively).
CONCLUSIONS
Levels of urea, uric acid, magnesium and fluoride in saliva can be associated with the course of iNS. Salivary levels of peroxidase and magnesium can be related to the phase of the disease. However, the measurements of these parameters cannot be useful as a noninvasive tool in diagnosing iNS and the phase of the disease.
Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Dental Caries; Female; Humans; Male; Nephrotic Syndrome; Peroxidase; Saliva
PubMed: 33413282
DOI: 10.1186/s12903-020-01375-1 -
Nature Communications May 2022Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin...
Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin depolymerization. A class of peptoid-based peroxidase mimetics with tunable catalytic activity and high stability is developed by constructing peptoids and hemins into self-assembled crystalline nanomaterials. By varying peptoid side chain chemistry to tailor the microenvironment of active sites, these self-assembled peptoid/hemin nanomaterials (Pep/hemin) exhibit highly modulable catalytic activities toward two lignin model substrates 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 3,3',5,5'-tetramethylbenzidine. Among them, a Pep/hemin complex containing the pyridyl side chain showed the best catalytic efficiency (V/K = 5.81 × 10 s). These Pep/hemin catalysts are highly stable; kinetics studies suggest that they follow a peroxidase-like mechanism. Moreover, they exhibit a high efficacy on depolymerization of a biorefinery lignin. Because Pep/hemin catalysts are highly robust and tunable, we expect that they offer tremendous opportunities for lignin valorization to high value products.
Topics: Biomimetics; Coloring Agents; Hemin; Lignin; Peptoids; Peroxidase; Peroxidases
PubMed: 35641490
DOI: 10.1038/s41467-022-30285-9 -
Expert Opinion on Therapeutic Targets Jul 2020Coronary artery disease (CAD) poses significant morbidity and mortality globally. Despite significant advances in treatment interventions, residual cardiovascular risks... (Review)
Review
INTRODUCTION
Coronary artery disease (CAD) poses significant morbidity and mortality globally. Despite significant advances in treatment interventions, residual cardiovascular risks remain unchecked. Recent clinical trials have shed light on the potential therapeutic benefits of targeting anti-inflammatory pathways. Myeloperoxidase (MPO) plays an important role in atherosclerotic plaque formation and destabilization of the fibrous cap; both increase the risk of atherosclerotic cardiovascular disease and especially CAD.
AREAS COVERED
This article examines the role of MPO in the pathogenesis of atherosclerotic CAD and the mechanistic data from several key therapeutic drug targets. There have been numerous interesting studies on prototype compounds that directly or indirectly attenuate the enzymatic activities of MPO, and subsequently exhibit atheroprotective effects; these include aminobenzoic acid hydrazide, ferulic acid derivative (INV-315), thiouracil derivatives (PF-1355 and PF-06282999), 2-thioxanthines derivative (AZM198), triazolopyrimidines, acetaminophen, N-acetyl lysyltyrosylcysteine (KYC), flavonoids, and alternative substrates such as thiocyanate and nitroxide radical.
EXPERT OPINION
Future investigations must determine if the cardiovascular benefits of direct systemic inhibition of MPO outweigh the risk of immune dysfunction, which may be less likely to arise with alternative substrates or MPO inhibitors that selectively attenuate atherogenic effects of MPO.
Topics: Animals; Anti-Inflammatory Agents; Coronary Artery Disease; Enzyme Inhibitors; Humans; Molecular Targeted Therapy; Peroxidase; Plaque, Atherosclerotic
PubMed: 32336171
DOI: 10.1080/14728222.2020.1762177 -
International Journal of Molecular... Apr 2023Phenols are widely used in industries despite their toxicity, which requires governments to limit their concentration in water to 5 mg/L before discharge to the city...
Phenols are widely used in industries despite their toxicity, which requires governments to limit their concentration in water to 5 mg/L before discharge to the city sewer. Thus, it is essential to develop a rapid, simple, and low-cost detection method for phenol. This study explored two pathways of peroxidase immobilization to develop a phenol detection system: peroxidase encapsulation into polyelectrolyte microcapsules and peroxidase captured by CaCO. The encapsulation of peroxidase decreased enzyme activity by 96%; thus, this method cannot be used for detection systems. The capturing process of peroxidase by CaCO microspherulites did not affect the maximum reaction rate and the Michaelis constant of peroxidase. The native peroxidase-Vmax = 109 µM/min, Km = 994 µM; CaCO-peroxidase-Vmax = 93.5 µM/min, Km = 956 µM. Ultimately, a reusable phenol detection system based on CaCO microparticles with immobilized peroxidase was developed, capable of detecting phenol in the range of 700 ng/mL to 14 µg/mL, with an error not exceeding 5%, and having a relatively low cost and production time. The efficiency of the system was confirmed by determining the content of phenol in a paintwork product.
Topics: Phenol; Peroxidase; Phenols; Peroxidases; Enzymes, Immobilized; Horseradish Peroxidase
PubMed: 37047739
DOI: 10.3390/ijms24076766 -
The New Phytologist Mar 2016Higher plants contain plant-specific peroxidases (class III peroxidase; Prxs) that exist as large multigene families. Reverse genetic studies to characterize the... (Review)
Review
Higher plants contain plant-specific peroxidases (class III peroxidase; Prxs) that exist as large multigene families. Reverse genetic studies to characterize the function of each Prx have revealed that Prxs are involved in lignification, cell elongation, stress defense and seed germination. However, the underlying mechanisms associated with plant phenotypes following genetic engineering of Prx genes are not fully understood. This is because Prxs can function as catalytic enzymes that oxidize phenolic compounds while consuming hydrogen peroxide and/or as generators of reactive oxygen species. Moreover, biochemical efforts to characterize Prxs responsible for lignin polymerization have revealed specialized activities of Prxs. In conclusion, not only spatiotemporal regulation of gene expression and protein distribution, but also differentiated oxidation properties of each Prx define the function of this class of peroxidases.
Topics: Free Radicals; Lignin; Peroxidase; Polymerization; Reverse Genetics
PubMed: 26542837
DOI: 10.1111/nph.13738 -
Pharmacology & Therapeutics Aug 2022Myeloperoxidase is a heme-peroxidase which makes up approximately 5% of the total dry cell weight of neutrophils where it is predominantly found in the primary... (Review)
Review
Myeloperoxidase is a heme-peroxidase which makes up approximately 5% of the total dry cell weight of neutrophils where it is predominantly found in the primary (azurophilic) granules. Other cell types, such as monocytes and certain macrophage subpopulations also contain myeloperoxidase, but to a much lesser extent. Initially, the function of myeloperoxidase had been mainly associated with its ability as a catalyzer of reactive oxidants that help to clear pathogens. However, over the past years non-canonical functions of myeloperoxidase have been described both in health and disease. Attention has been specially focused on inflammatory diseases, in which an exacerbate infiltration of leukocytes can favor a poorly-controlled production and release of myeloperoxidase and its oxidants. There is compelling evidence that myeloperoxidase derived oxidants contribute to tissue damage and the development and propagation of acute and chronic vascular inflammation. Recently, neutrophils have attracted much attention within the large diversity of innate immune cells that are part of the tumor microenvironment. In particular, neutrophil-derived myeloperoxidase may play an important role in cancer development and progression. This review article aims to provide a comprehensive overview of the roles of myeloperoxidase in the development and progression of cancer. We propose future research approaches and explore prospects of inhibiting myeloperoxidase as a strategy to fight against cancer.
Topics: Humans; Inflammation; Neoplasms; Neutrophils; Oxidants; Peroxidase; Tumor Microenvironment
PubMed: 34890688
DOI: 10.1016/j.pharmthera.2021.108052 -
Free Radical Biology & Medicine Aug 2021The heme peroxidase family generates a battery of oxidants both for synthetic purposes, and in the innate immune defence against pathogens. Myeloperoxidase (MPO) is the... (Review)
Review
The heme peroxidase family generates a battery of oxidants both for synthetic purposes, and in the innate immune defence against pathogens. Myeloperoxidase (MPO) is the most promiscuous family member, generating powerful oxidizing species including hypochlorous acid (HOCl). Whilst HOCl formation is important in pathogen removal, this species is also implicated in host tissue damage and multiple inflammatory diseases. Significant oxidant formation and damage occurs extracellularly as a result of MPO release via phagolysosomal leakage, cell lysis, extracellular trap formation, and inappropriate trafficking. MPO binds strongly to extracellular biomolecules including polyanionic glycosaminoglycans, proteoglycans, proteins, and DNA. This localizes MPO and subsequent damage, at least partly, to specific sites and species, including extracellular matrix (ECM) components and plasma proteins/lipoproteins. Biopolymer-bound MPO retains, or has enhanced, catalytic activity, though evidence is also available for non-catalytic effects. These interactions, particularly at cell surfaces and with the ECM/glycocalyx induce cellular dysfunction and altered gene expression. MPO binds with higher affinity to some damaged ECM components, rationalizing its accumulation at sites of inflammation. MPO-damaged biomolecules and fragments act as chemo-attractants and cell activators, and can modulate gene and protein expression in naïve cells, consistent with an increasing cycle of MPO adhesion, activity, damage, and altered cell function at sites of leukocyte infiltration and activation, with subsequent tissue damage and dysfunction. MPO levels are used clinically both diagnostically and prognostically, and there is increasing interest in strategies to prevent MPO-mediated damage; therapeutic aspects are not discussed as these have been reviewed elsewhere.
Topics: Humans; Hypochlorous Acid; Inflammation; Oxidants; Oxidation-Reduction; Peroxidase
PubMed: 34246778
DOI: 10.1016/j.freeradbiomed.2021.07.007