Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions

2011 ◽  
Vol 392 (3) ◽  
Author(s):  
Andrzej Kozik ◽  
Anna Golda ◽  
Pawel Mak ◽  
Piotr Suder ◽  
Jerzy Silberring ◽  
...  
Keyword(s):  
Hypochlorous Acid ◽  
Methionine Sulfoxide ◽  
Peptide Bond ◽  
Chloride Ions ◽  
Protein Chemistry ◽  
Oxygen Species ◽  
Chloride System ◽  
Inflammatory Reactions ◽  
Oxidative Inactivation ◽  
Vasoactive Peptides

Abstract Bradykinin-related vasoactive peptides (kinins) are important mediators of local and systemic inflammatory reactions. However, at local inflammatory foci, the production of kinins from proteinaceous precursors (kininogens) can be affected by reactive oxygen species released by phagocyte cells. One of the predominant oxidants at these places is hypochlorous acid which is formed from hydrogen peroxide and chloride ions by neutrophil myeloperoxidase. In this study, inactivation of human kininogens after oxidation with the myeloperoxidase-H2O2-chloride system was observed and analyzed by protein chemistry methods. The kinin release from oxidized kininogens by major kinin-producing enzymes, plasma and tissue kallikreins, proceed with a very low rate. This effect was assigned to apparent inability of kallikreins to process the kinin N-terminus owing to the conversion of the adjacent Met-361 residue to methionine sulfoxide. Additionally, the oxidized high-molecular mass kininogen lost its natural ability to bind plasma prekallikrein. This effect was assigned to the oxidation of Trp-569 residue within the prekallikrein-binding region which is subsequently destructed owing to cleavage of the peptide bond after that residue. One possible pathophysiological consequence of the described effects on kininogens could be the impairment of the normal assembly and triggering of the kinin-forming system on defense cell surfaces.

Oxidative Modification of Von Willebrand Factor Inhibits Its Cleavage by ADAMTS13

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3921-3921
Author(s):  
Junmei Chen ◽  
Xiaoyun Fu ◽  
Minhua Ling ◽  
Brad McMullen ◽  
John Kulman ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Amino Acid ◽  
Hypochlorous Acid ◽  
Methionine Sulfoxide ◽  
Peptide Bond ◽  
Chloride Ions ◽  
Cleavage Product ◽  
Oxidative Modification ◽  
Activated Neutrophils ◽  
Methionine Residues

Abstract During inflammation, activated neutrophils go through the oxidative burst, releasing various oxidants, including superoxide radical, hydrogen peroxide, and hypochlorous acid (HOCl). Activated neutrophils also release myeloperoxidase (MPO), which generates HOCl from hydrogen peroxide and chloride ions. HOCl preferentially oxidizes cysteine and methionine residues to cysteine sulfenic acid and methionine sulfoxide, respectively, at rates ~100 times faster than it oxidizes tyrosine, another commonly oxidized amino acid. HOCl can also oxidize tyrosine to chlorotyrosine. Of great interest in this regard is the fact that the ADAMTS13 cleavage site in VWF, the Tyr1605–Met1606 peptide bond, contains two residues that are potential targets for myeloperoxidase-mediated oxidation. Given previous studies from our laboratory that VWF cleavage by ADAMTS13 is inhibited by oxidants, we hypothesized that neutrophil oxidants might oxidize either or both of these two amino acid residues and thereby potentially inhibit ADAMTS13-mediated cleavage. We tested our hypothesis using a peptide substrate for ADAMTS13 based on the VWF A2 sequence Leu1591–Arg1668. We incubated the VWF A2 peptide either without HOCl or with 25 or 75 μM HOCl, followed by quenching the oxidant with free methionine. The peptides were then incubated with purified recombinant ADAMTS13 and the reaction sampled every 15 min for one hour. We analyzed the cleavage reaction in two ways: by electrophoretic separation on a Tricine gel and densitometric quantification of the cleavage product, and by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) to determine the location and extent of oxidative modification and quantity of the cleavage product. We found that, after exposure to 75 μM HOCl, the A2 peptide contained methionine sulfoxide at position 1606 in 99% of the molecules in the sample, whereas only 0.3% contained both chlorotyrosine at position 1605 and methionine sulfoxide at 1606. The rate of substrate cleavage by ADAMTS13 was markedly reduced with oxidation, as measured by both assays, with the rate for the peptide treated with 75 μM HOCl being only 20% of that of the non-oxidized peptide. Taken together, these findings suggest that oxidants released by activated neutrophils during inflammation have a prothrombotic effect, mediated at least in part by inhibition of VWF cleavage by ADAMTS13.

scholarly journals Research Progress of Small Molecule Fluorescent Probes for Detecting Hypochlorite

Sensors ◽  
2021 ◽  
Vol 21 (19) ◽  
pp. 6326
Author(s):  
Zhi-Guo Song ◽  
Qing Yuan ◽  
Pengcheng Lv ◽  
Kun Chen
Keyword(s):  
Fluorescent Probes ◽  
High Selectivity ◽  
Hypochlorous Acid ◽  
High Sensitivity ◽  
Chloride Ions ◽  
Research Progress ◽  
Oxygen Species ◽  
Low Toxicity ◽  
Fluorescent Probe Method

Hypochlorous acid (HOCl) generates from the reaction between hydrogen peroxide and chloride ions via myeloperoxidase (MPO)-mediated in vivo. As very important reactive oxygen species (ROS), hypochlorous acid (HOCl)/hypochlorite (OCl−) play a crucial role in a variety of physiological and pathological processes. However, excessive or misplaced production of HOCl/OCl− can cause variety of tissue damage and human diseases. Therefore, rapid, sensitive, and selective detection of OCl− is very important. In recent years, the fluorescent probe method for detecting hypochlorous acid has been developed rapidly due to its simple operation, low toxicity, high sensitivity, and high selectivity. In this review, the progress of recently discovered fluorescent probes for the detection of hypochlorous acid was summarized with the aim to provide useful information for further design of better fluorescent probes.

scholarly journals The Responses of Bioactive Betanin Pigment and Its Derivatives from a Red Beetroot (Beta vulgaris L.) Betalain-Rich Extract to Hypochlorous Acid

2021 ◽  
Vol 22 (3) ◽  
pp. 1155
Author(s):  
Karolina Starzak ◽  
Katarzyna Sutor ◽  
Tomasz Świergosz ◽  
Boris Nemzer ◽  
Zbigniew Pietrzkowski ◽  
...  
Keyword(s):  
Beta Vulgaris ◽  
Hypochlorous Acid ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Oxygen Species ◽  
Plant Pigments ◽  
Important Food ◽  
Inflammatory Conditions ◽  
Ph Range

Neutrophils produce hypochlorous acid (HOCl) as well as other reactive oxygen species as part of a natural innate immune response in the human body; however, excessive levels of HOCl can ultimately be detrimental to health. Recent reports suggest that betacyanin plant pigments can act as potent scavengers of inflammatory factors and are notably effective against HOCl. Comparison of the in vitro anti-hypochlorite activities of a novel betalain-rich red beetroot (Beta vulgaris L.) extract with its pure betalainic pigments revealed that the extract had the highest anti-hypochlorite activity, far exceeding the activity of all of the betalainic derivatives and selected reference antioxidants. This suggests that it may be an important food-based candidate for management of inflammatory conditions induced by excessive HOCl production. Among all pigments studied, betanidin exhibited the highest activity across the pH range.

scholarly journals Glutathione Participation in the Prevention of Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1220
Author(s):  
Deyamira Matuz-Mares ◽  
Héctor Riveros-Rosas ◽  
María Magdalena Vilchis-Landeros ◽  
Héctor Vázquez-Meza
Keyword(s):  
Cardiovascular Diseases ◽  
Superoxide Anion ◽  
Reactive Nitrogen Species ◽  
Hypochlorous Acid ◽  
Reduced Glutathione ◽  
Heart Diseases ◽  
Reactive Species ◽  
Oxygen Species ◽  
Cardiovascular Pathologies

Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. In this review, we will address the role of glutathione, its synthesis in both the heart and the liver, and its importance in preventing or reducing deleterious ROS effects in cardiovascular diseases.

scholarly journals Acetylated Thioredoxin Reductase 1 Resists Oxidative Inactivation

2021 ◽  
Vol 9 ◽  
Author(s):  
David. E. Wright ◽  
Nikolaus Panaseiko ◽  
Patrick O’Donoghue
Keyword(s):  
Oxidative Stress ◽  
Thioredoxin Reductase ◽  
Oxygen Species ◽  
Site Specific ◽  
Oxidative Inactivation ◽  
Thioredoxin Reductase 1 ◽  
Lysine Residues ◽  
Canonical Amino Acid ◽  
Genetic Code Expansion ◽  
Low Activity

Thioredoxin Reductase 1 (TrxR1) is an enzyme that protects human cells against reactive oxygen species generated during oxidative stress or in response to chemotherapies. Acetylation of TrxR1 is associated with oxidative stress, but the function of TrxR1 acetylation in oxidizing conditions is unknown. Using genetic code expansion, we produced recombinant and site-specifically acetylated variants of TrxR1 that also contain the non-canonical amino acid, selenocysteine, which is essential for TrxR1 activity. We previously showed site-specific acetylation at three different lysine residues increases TrxR1 activity by reducing the levels of linked dimers and low activity TrxR1 tetramers. Here we use enzymological studies to show that acetylated TrxR1 is resistant to both oxidative inactivation and peroxide-induced multimer formation. To compare the effect of programmed acetylation at specific lysine residues to non-specific acetylation, we produced acetylated TrxR1 using aspirin as a model non-enzymatic acetyl donor. Mass spectrometry confirmed aspirin-induced acetylation at multiple lysine residues in TrxR1. In contrast to unmodified TrxR1, the non-specifically acetylated enzyme showed no loss of activity under increasing and strongly oxidating conditions. Our data suggest that both site-specific and general acetylation of TrxR1 regulate the enzyme’s ability to resist oxidative damage.

scholarly journals HypVW is an HOCl-Sensing Two Component System in Escherichia coli

2021 ◽  
Author(s):  
Sara El Hajj ◽  
Camille Henry ◽  
Alexandra Vergnes ◽  
Laurent Loiseau ◽  
Brasseur Gael ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hypochlorous Acid ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Bacterial Cells ◽  
E Coli ◽  
Two Component ◽  
Redox Switch ◽  
Two Component Systems ◽  
Methionine Residues

Two component systems (TCS) are signalling pathways that allow bacterial cells to sense, respond and adapt to fluctuating environments. Among the classical TCS of Escherichia coli, YedVW has been recently showed to be involved in the regulation of msrPQ, encoding for the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of msrPQ in a YedVW dependant manner, whereas H2O2, NO and paraquat (a superoxide generator) do not. Therefore, YedV appears to be an HOCl-sensing histidine kinase. Based on this finding, we proposed to rename this system HypVW.  Moreover, using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HypV (formerly YedV) are important for its activity. Given that HOCl oxidizes preferentially Met residues, we bring evidences that HypV could be activated via the reversible oxidation of its methionine residues, thus conferring to MsrPQ a role in switching HypVW off. Based on these results, we propose that the activation of HypV by HOCl could occur through a Met redox switch. HypVW appears to be the first characterized TCS able to detect HOCl in E. coli. This study represents an important step in understanding the mechanisms of reactive chlorine species resistance in prokaryotes.

HprSR is a Reactive Chlorine Species-Sensing, Two-Component System in Escherichia coli

2021 ◽  
Author(s):  
Sara El Hajj ◽  
Camille Henry ◽  
Camille Andrieu ◽  
Alexandra Vergnes ◽  
Laurent Loiseau ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hypochlorous Acid ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Repair System ◽  
Bacterial Cells ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Redox Switch

Two-component systems (TCS) are signalling pathways that allow bacterial cells to sense, respond and adapt to fluctuating environments. Among the classical TCS of Escherichia coli , HprSR has recently been shown to be involved in the regulation of msrPQ , which encodes the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of msrPQ in an HprSR-dependant manner, whereas H 2 O 2 , NO and paraquat (a superoxide generator) do not. Therefore, HprS appears to be an HOCl-sensing histidine kinase. Using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HprS are important for its activity: as HOCl preferentially oxidizes Met residues, we provide evidence that HprS could be activated via the reversible oxidation of its methionine residues, meaning that MsrPQ plays a role in switching HprSR off. We propose that the activation of HprS by HOCl could occur through a Met redox switch. HprSR appears to be the first characterized TCS able to detect reactive chlorine species (RCS) in E. coli . This study represents an important step towards understanding the mechanisms of RCS resistance in prokaryotes. IMPORTANCE Understanding how bacteria respond to oxidative stress at the molecular level is crucial in the fight against pathogens. HOCl is one of the most potent industrial and physiological microbiocidal oxidants. Therefore bacteria have developed counterstrategies to survive HOCl-induced stress. Over the last decade, important insights into these bacterial protection factors have been obtained. Our work establishes HprSR as a reactive chlorine species-sensing, two-component system in Escherichia coli MG1655, which regulates the expression of MsrPQ, a repair system for HOCl-oxidized proteins. Moreover we provide evidence suggesting that HOCl could activate HprS through a methionine redox switch.

Nonspecific Chlorination of Organics: a Chemistry Unique to Human Industry? (Putting Kraft Mill AOX Emissions into Perspective)

1998 ◽  
Vol 33 (3) ◽  
pp. 347-362
Author(s):  
Frederick Archibald ◽  
Loredana Valeanu ◽  
Gunther Leichtle ◽  
Benoit Guilbault
Keyword(s):  
Hypochlorous Acid ◽  
Higher Plants ◽  
Chloride Ions ◽  
Soil Extracts ◽  
Wide Range ◽  
Mammalian Blood ◽  
Kraft Mill ◽  
Natural Result ◽  
Living Organisms ◽  
Work Done

Abstract To counter the claim that all biotreated organochlorine (AOX) emissions from modern kraft mills are unnatural and inherently hazardous, it has been argued that over 2400 different AOX compounds are now known to be produced by living organisms. This is an invalid rationale. These 2400 natural compounds are mostly specific halometabolites — each is produced as a large number of identical molecules by a specific enzyme-mediated mechanism. In contrast, in a kraft mill bleachery, heterogeneous wood derivatives are non-specifically chlorinated by hypochlorous acid (HOCl) or hypochlorite ion (OCl-) to produce mixtures containing hundreds of different AOX species. It is therefore much more reasonable to compare mill-derived AOX to other human and natural sources of OCl-/HOCl-generated non-specific AOX. Chloroperoxidase (CPO)-type enzymes naturally produce HOCl and OCl-from common chloride ions and hydrogen peroxide (H2O2). They have now been demonstrated in bacteria, fungi, algae, lichens, higher plants and animals. We demonstrate that a common fungal CPO can, when applied to soil extracts, lignins, cellulosics, tannins and natural lake water organics, rapidly generate nonspecific AOX. In agreement with earlier work done in other geographic areas, AOX was found in all of a wide range of samples from the Montreal region, both from urban and relatively remote pristine lakes and woodlands. Much of it is almost certainly produced via nonspecific HOCl/OCl- chlorination. Finally, we demonstrate that nonspecific AOX is produced by a CPO in mammalian blood as the natural result of the body's immune system fighting infections. Thus, HOCl/OCl- based production of AOX from mixtures of organic molecules is seen to be a common occurrence in nature as well as a product of human technology.

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