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Nature Reviews. Disease Primers Aug 2020The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are... (Review)
Review
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA or ANCA, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Diagnostic Imaging; Humans; Immunosuppressive Agents; Myeloblastin; Peroxidase; Prognosis; Risk Factors
PubMed: 32855422
DOI: 10.1038/s41572-020-0204-y -
European Respiratory Review : An... Dec 2021Over the past three decades, an increasing number of publications have reported the association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic... (Review)
Review
Over the past three decades, an increasing number of publications have reported the association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic antibody (ANCA) or ANCA-associated vasculitis (AAV). With this increased awareness, we have reviewed the literature to date and provide an update in this narrative review. The vast majority of cases of ILD have been shown to be in the setting of positive anti-myeloperoxidase antibody and can be present in up to 45% of patients of microscopic polyangiitis, though cases of ILD associated with proteinase 3 ANCA have rarely been reported. Pulmonary fibrosis and ANCA positivity can occur with or without systemic involvement. The pathogenetic mechanisms establishing the relationship between ANCA and the development of pulmonary fibrosis remain unclear. Histologic and radiographic features of ANCA-ILD most commonly reveal usual interstitial pneumonia or non-specific interstitial pneumonia patterns, though other atypical features such as bronchiolitis have been described. ILD in the setting of AAV has been associated with worse outcomes, and thus early identification and treatment in these patients is appropriate. We advocate that ANCA antibody testing be performed as a baseline evaluation in patients presenting with idiopathic interstitial pneumonia. Suggested treatment of ANCA-ILD includes immunosuppression and/or antifibrotic agents, though supporting data and clinical trials to substantiate use of these therapies are needed.
Topics: Antibodies, Antineutrophil Cytoplasmic; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Peroxidase
PubMed: 34750115
DOI: 10.1183/16000617.0123-2021 -
International Journal of Molecular... Apr 2023Innate and adaptive immune responses comprise a complex network of protein-protein and protein-cell interactions that regulates commensal flora and protects organisms...
Innate and adaptive immune responses comprise a complex network of protein-protein and protein-cell interactions that regulates commensal flora and protects organisms from foreign pathogens and transformed (proliferating) host cells under physiological conditions such as pregnancy, growth and development as well as formulating a response pathological challenge [...].
Topics: Immunity, Innate; Peroxidase; Humans; Health
PubMed: 37175430
DOI: 10.3390/ijms24097725 -
Clinical Chemistry and Laboratory... Jul 2023Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be... (Review)
Review
Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be aware of these pitfalls since they often lead to medical overconsumption or incorrect diagnosis. Pre-analytical issues (use of vacuum tubes or urine tubes containing preservatives) can affect test results. In routine clinical laboratories, hematuria can be assayed using either chemical (test strips) or particle-counting techniques. In cases of doubtful results, Munchausen syndrome or adulteration of the urine specimen should be excluded. Pigmenturia (caused by the presence of dyes, urinary metabolites such as porphyrins and homogentisic acid, and certain drugs in the urine) can be easily confused with hematuria. The peroxidase activity (test strip) can be positively affected by the presence of non-Hb peroxidases (e.g. myoglobin, semen peroxidases, bacterial, and vegetable peroxidases). Urinary pH, haptoglobin concentration, and urine osmolality may affect specific peroxidase activity. The implementation of expert systems may be helpful in detecting preanalytical and analytical errors in the assessment of hematuria. Correcting for dilution using osmolality, density, or conductivity may be useful for heavily concentrated or diluted urine samples.
Topics: Humans; Hematuria; Peroxidase; Hemoglobins; Erythrocytes; Osmolar Concentration
PubMed: 37079906
DOI: 10.1515/cclm-2023-0260 -
Cells May 2022Peroxiredoxins are multifunctional enzymes that play a key role in protecting cells from stresses and maintaining the homeostasis of many cellular processes.... (Review)
Review
Peroxiredoxins are multifunctional enzymes that play a key role in protecting cells from stresses and maintaining the homeostasis of many cellular processes. Peroxiredoxins were firstly identified as antioxidant enzymes that can be found in all living organisms. Later studies demonstrated that peroxiredoxins also act as redox signaling regulators, chaperones, and proinflammatory factors and play important roles in oxidative defense, redox signaling, protein folding, cycle cell progression, DNA integrity, inflammation, and carcinogenesis. The versatility of peroxiredoxins is mainly based on their unique active center cysteine with a wide range of redox states and the ability to switch between low- and high-molecular-weight species for regulating their peroxidase and chaperone activities. Understanding the molecular mechanisms of peroxiredoxin in these processes will allow the development of new approaches to enhance longevity and to treat various cancers. In this article, we briefly review the history of peroxiredoxins, summarize recent advances in our understanding of peroxiredoxins in aging- and cancer-related biological processes, and discuss the future perspectives of using peroxiredoxins in disease diagnostics and treatments.
Topics: Antioxidants; Humans; Neoplasms; Oxidation-Reduction; Peroxidase; Peroxiredoxins
PubMed: 35681467
DOI: 10.3390/cells11111772 -
Archives of Biochemistry and Biophysics Mar 2018Members of Chordata peroxidase subfamily [1] expressed in mammals, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid... (Review)
Review
Members of Chordata peroxidase subfamily [1] expressed in mammals, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO), express conserved motifs around the heme prosthetic group essential for their activity, a calcium-binding site, and at least two covalent bonds linking the heme group to the protein backbone. Although most studies of the biosynthesis of these peroxidases have focused on MPO, many of the features described occur during biosynthesis of other members of the protein subfamily. Whereas MPO biosynthesis includes events typical for proteins generated in the secretory pathway, the importance and consequences of heme insertion are events uniquely associated with peroxidases. This Review summarizes decades of work elucidating specific steps in the biosynthetic pathway of human MPO. Discussion includes cotranslational glycosylation and subsequent modifications of the N-linked carbohydrate sidechains, contributions by molecular chaperones in the endoplasmic reticulum, cleavage of the propeptide from proMPO, and proteolytic processing of protomers and dimerization to yield mature MPO. Parallels between the biosynthesis of MPO and TPO as well as the impact of inherited mutations in the MPO gene on normal biosynthesis will be summarized. Lastly, specific gaps in our knowledge revealed by this review of our current understanding will be highlighted.
Topics: Binding Sites; Calcium; Dimerization; Endoplasmic Reticulum; Eosinophil Peroxidase; Glycosylation; Heme; Humans; Iodide Peroxidase; Lactoperoxidase; Peroxidase; Proteolysis
PubMed: 29408362
DOI: 10.1016/j.abb.2018.02.001 -
Free Radical Biology & Medicine Mar 2022Heme-containing peroxidases catalyze the oxidation of a variety of substrates by consuming hydrogen peroxide (HO), and play diversified roles in physiology and pathology... (Review)
Review
Heme-containing peroxidases catalyze the oxidation of a variety of substrates by consuming hydrogen peroxide (HO), and play diversified roles in physiology and pathology including innate immunity, the synthesis of thyroid hormone and the extracellular matrix, as well as the pathogenesis of several inflammatory diseases. Peroxidasin (PXDN), also known as Vascular Peroxidase-1 (VPO1), is a newly identified peroxidase and expresses in multiple cells and tissues including cardiovascular system and the lung. Recent studies imply its roles in the innate immunity, cardiovascular physiology and diseases, and extracellular matrix formation. Studies on the role of PXDN in human diseases are entering a new and exciting stage, and this review provides the insights into this emerging field of PXDN.
Topics: Animals; Deoxyribonucleosides; Extracellular Matrix Proteins; Humans; Hydrogen Peroxide; Mammals; Peroxidase; Peroxidases; Purine Nucleosides; Peroxidasin
PubMed: 35219848
DOI: 10.1016/j.freeradbiomed.2022.02.026 -
Antioxidants & Redox Signaling Mar 2018Peroxiredoxins (Prxs) are thiol peroxidases with multiple functions in the antioxidant defense and redox signaling network of the cell. Our progressing understanding... (Review)
Review
SIGNIFICANCE
Peroxiredoxins (Prxs) are thiol peroxidases with multiple functions in the antioxidant defense and redox signaling network of the cell. Our progressing understanding assigns both local and global significance to plant Prxs, which are grouped in four Prx types. In plants they are localized to the cytosol, mitochondrion, plastid, and nucleus. Antioxidant defense is fundamentally connected to redox signaling, cellular communication, and acclimation. The thiol-disulfide network is central part of the stress sensing and processing response and integrates information input with redox regulation. Recent Advances: Prxs function both as redox sensory system within the network and redox-dependent interactors. The processes directly or indirectly targeted by Prxs include gene expression, post-transcriptional reactions, including translation, post-translational regulation, and switching or tuning of metabolic pathways, and other cell activities. The most advanced knowledge is available for the chloroplast 2-CysPrx wherein recently a solid interactome has been defined. An in silico analysis of protein structure and coexpression reinforces new insights into the 2-CysPrx functionality.
CRITICAL ISSUES
Up to now, Prxs often have been investigated for local properties of enzyme activity. In vitro and ex vivo work with mutants will reveal the ability of Prxs to interfere with multiple cellular components, including crosstalk with Ca-linked signaling pathways, hormone signaling, and protein homeostasis.
FUTURE DIRECTIONS
Complementation of the Prxs knockout lines with variants that mimic specific states, namely devoid of peroxidase activity, lacking the oligomerization ability, resembling the hyperoxidized decamer, or with truncated C-terminus, should allow dissecting the roles as thiol peroxidase, oxidant, interaction partner, and chaperone. Antioxid. Redox Signal. 28, 609-624.
Topics: Antioxidants; Chloroplasts; Molecular Chaperones; Oxidation-Reduction; Peroxidase; Peroxiredoxins; Photosynthesis; Plants
PubMed: 28594234
DOI: 10.1089/ars.2017.7164 -
International Journal of Molecular... Oct 2018The major enzymes involved in lignin degradation are laccase, class II peroxidases (lignin peroxidase, manganese peroxidase, and versatile peroxidase) and dye... (Review)
Review
The major enzymes involved in lignin degradation are laccase, class II peroxidases (lignin peroxidase, manganese peroxidase, and versatile peroxidase) and dye peroxidase, which use an oxidative or peroxidative mechanism to deconstruct the complex and recalcitrant lignin. Laccase and manganese peroxidase directly oxidize phenolic lignin components, while lignin peroxidase and versatile peroxidase can act on the more recalcitrant non-phenolic lignin compounds. Mediators or co-oxidants not only increase the catalytic ability of these enzymes, but also largely expand their substrate scope to those with higher redox potential or more complicated structures. Neither laccase nor the peroxidases are stringently selective of substrates. The promiscuous nature in substrate preference can be employed in detoxification of a range of organics.
Topics: Biocatalysis; Biodegradation, Environmental; Hydrolysis; Lignin; Oxidation-Reduction; Peroxidase
PubMed: 30373305
DOI: 10.3390/ijms19113373 -
Molecules (Basel, Switzerland) Oct 2018The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase... (Review)
Review
The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome /cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes.
Topics: Catalytic Domain; Eosinophil Peroxidase; Free Radicals; Heme; Humans; Hydrogen Peroxide; Lactoperoxidase; Oxidation-Reduction; Oxidative Stress; Peroxidase; Peroxidases
PubMed: 30297621
DOI: 10.3390/molecules23102561