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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 -
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 -
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 -
Biomolecules Jul 2021Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as... (Review)
Review
Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as photodynamic therapy (PDT) and radio therapy (RT), are strongly oxygen-dependent, which hinders their practical applications. Later on, several strategies were developed to overcome tumor hypoxia, such as oxygen carrier nanomaterials and oxygen generated nanomaterials. Among these, oxygen species generation on nanozymes, especially catalase (CAT) mimetic nanozymes, convert endogenous hydrogen peroxide (HO) to oxygen (O) and peroxidase (POD) mimetic nanozymes converts endogenous HO to water (HO) and reactive oxygen species (ROS) in a hypoxic tumor microenvironment is a fascinating approach. The present review provides a detailed examination of past, present and future perspectives of POD mimetic nanozymes for effective oxygen-dependent cancer phototherapeutics.
Topics: Animals; Biomimetic Materials; Humans; Nanostructures; Neoplasms; Oxygen; Peroxidase; Photochemotherapy; Tumor Hypoxia; Tumor Microenvironment
PubMed: 34356639
DOI: 10.3390/biom11071015 -
The Journal of Biological Chemistry Jan 1951
Topics: Amine Oxidase (Copper-Containing); Amines; Coloring Agents; Oxidoreductases; Peroxidase; Peroxidases
PubMed: 14814121
DOI: No ID Found -
Redox Biology May 2020Cytoglobin is an evolutionary ancient hemoglobin with poor functional annotation. Rather than constrained to penta coordination, cytoglobin's heme iron may exist either... (Review)
Review
Cytoglobin is an evolutionary ancient hemoglobin with poor functional annotation. Rather than constrained to penta coordination, cytoglobin's heme iron may exist either as a penta or hexacoordinated arrangement when exposed to different intracellular environments. Two cysteine residues at the surface of the protein form an intramolecular disulfide bond that regulates iron coordination, ligand binding, and peroxidase activity. Overall, biochemical results do not support a role for cytoglobin as a direct antioxidant enzyme that scavenges hydrogen peroxide because the rate of the reaction of cytoglobin with hydrogen peroxide is several orders of magnitude slower than metal and thiol-based peroxidases. Thus, alternative substrates such as fatty acids have been suggested and regulation of nitric oxide bioavailability through nitric oxide dioxygenase and nitrite reductase activities has received experimental support. Cytoglobin is broadly expressed in connective, muscle, and nervous tissues. Rational for differential cellular distribution is poorly understood but inducibility in response to hypoxia is one of the most established features of cytoglobin expression with regulation through the transcription factor hypoxia-inducible factor (HIF). Phenotypic characterization of cytoglobin deletion in the mouse have indicated broad changes that include a heightened inflammatory response and fibrosis, increase tumor burden, cardiovascular dysfunction, and hallmarks of senescence. Some of these changes might be reversed upon inhibition of nitric oxide synthase. However, subcellular and molecular interactions have been seldom characterized. In addition, specific molecular mechanisms of action are still lacking. We speculate that cytoglobin functionality will extend beyond nitric oxide handling and will have to encompass indirect regulatory antioxidant and redox sensing functions.
Topics: Animals; Cytoglobin; Globins; Mice; Oxygenases; Peroxidase; Peroxidases
PubMed: 32087552
DOI: 10.1016/j.redox.2020.101468 -
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 -
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 -
IUBMB Life May 2022Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin...
Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin in-vivo, where its redox activity leads to peroxidative damage of membrane lipids and proteins. Spectrin, the major component of the red blood cell (RBC) membrane skeleton, is known to interact with hemoglobin and, here this interaction is shown to increase hemoglobin peroxidase activity in the presence of reducing substrate ABTS (2', 2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid). It is also shown that in the absence of reducing substrate, spectrin forms covalently cross-linked aggregates with hemoglobin which display no peroxidase activity. This may have implications in the clearance of ROS and limiting peroxidative damage. Spectrin is found to modulate the peroxidase activity of different hemoglobin variants like A, E, and S, and of isolated globin chains from each of these variants. This may be of importance in disease states like sickle cell disease and HbE-β-thalassemia, where increased oxidative damage and free globin subunits are present due to the defects inherent in the hemoglobin variants associated with these diseases. This hypothesis is corroborated by lipid peroxidation experiments. The modulatory role of spectrin is shown to extend to other heme proteins, namely catalase and cytochrome-c. Experiments with free heme and Raman spectroscopy of heme proteins in the presence of spectrin show that structural alterations occur in the heme moiety of the heme proteins on spectrin binding, which may be the structural basis of increased enzyme activity.
Topics: Antioxidants; Catalase; Heme; Hemeproteins; Hemoglobins; Peroxidase; Peroxidases; Reactive Oxygen Species; Spectrin
PubMed: 35184374
DOI: 10.1002/iub.2607