Disease relevance of hypochlorous acid

• Effects of the putative neutrophil-generated toxin, hypochlorous acid, on membrane permeability and transport systems of Escherichia coli [1].
• The data suggest that when PMN are stimulated, MPO released by degranulation reacts with H2O2 formed by the respiratory burst to oxidize chloride to a product (presumably hypochlorous acid) that is toxic to HIV-1 [2].
• The toxicity of hypochlorous acid (HOCl) generated from activated neutrophils has been associated with several pathological processes such as atherosclerosis [3].
• Advanced human atheroma contains high levels of the enzyme myeloperoxidase that produces the pro-oxidant species, hypochlorous acid (HOCl) [4].
• Immunostaining with an antibody to proteins modified by hypochlorous acid, a characteristic product of the enzyme, indicated that myeloperoxidase is enzymatically active in cases of acute liver injury and cirrhosis [5].

Psychiatry related information on hypochlorous acid

• A significant specific increase in the actin carbonyl content has been recently demonstrated in human brain regions severely affected by the Alzheimer's disease pathology, in postischemic isolated rat hearts, and in human intestinal cell monolayers following incubation with hypochlorous acid (HOCl) [6].

High impact information on hypochlorous acid

• Conversion of alpha-amino acids to aldehydes requires hypochlorous acid (HOCl), formed from H2O2 and chloride by myeloperoxidase [7].
• Indeed, brief exposure of polyetherurethane to activated human neutrophils, hypochlorous acid, or peroxynitrite produces modifications of the polymer similar to those found in vivo [8].
• Inhibition was blocked by adding catalase, an inhibitor of myeloperoxidase, or compounds that scavenge hypochlorous acid or chloramines [9].
• Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the alpha-1-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and alpha-1-PI were physically separated [10].
• We conclude that neutrophils can cooperatively use an oxidant with characteristics similar, if not identical, to hypochlorous acid and the lysosomal proteinase elastase to negate the protective effects of alpha-1-proteinase inhibitor in order to attack the subendothelial matrix [11].

Chemical compound and disease context of hypochlorous acid

• Nitrite-mediated protection against hypochlorous acid-induced chondrocyte toxicity: a novel cytoprotective role of nitric oxide in the inflamed joint [12]?
• Cytoprotection against neutrophil derived hypochlorous acid: a potential mechanism for the therapeutic action of 5-aminosalicylic acid in ulcerative colitis [13].
• 3-Chlorotyrosine, a bio-marker of hypochlorous acid (HOCl) in vivo, was reported to be substantially elevated in the Alzheimer's disease (AD) brains [14].
• Oxidation of Escherichia coli by hypochlorous acid (HOCl) or chloramine (NH2Cl) gives rise to massive hydrolysis of cytosolic nucleotide phosphoanhydride bonds, although no immediate change occurs in either the nucleotide pool size or the concentrations of extracellular end products of AMP catabolism [15].
• The purpose of this study was to investigate the effect of the oxidants hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) on the vulnerability of the myocardium to reperfusion-induced arrhythmias following global ischemia [16].

Biological context of hypochlorous acid

• Myeloperoxidase (MPO) catalyzes a reaction between chloride and hydrogen peroxide to generate hypochlorous acid and other reactive compounds that have been linked to DNA damage [17].
• Calcium homeostasis in rabbit ventricular myocytes. Disruption by hypochlorous acid and restoration by dithiothreitol [18].
• Somatic cell hybrids heterozygous at the emetine resistance locus (emtr/emt+) or the chromate resistance locus (chrr/chr+) are known to segregate the recessive drug resistance phenotype at high frequency [19].
• LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22) [20].
• Distinct modes of cell death induced by different reactive oxygen species: amino acyl chloramines mediate hypochlorous acid-induced apoptosis [21].

Anatomical context of hypochlorous acid

• An analysis of the process regulating the enzyme's activity revealed that the neutrophil MP was released from cells in a latent form whose activation was tightly linked to the generation of hypochlorous acid [22].
• These hypochlorous acid scavengers were also successful in inhibiting monocyte or granulocyte-mediated CEM cytotoxicity [23].
• The destruction of endothelial cells by the glucose oxidase-myeloperoxidase system was inhibited by the addition of hypochlorous acid scavengers [24].
• Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase [25].
• Oxidative degradation of biological substrates by hypochlorous acid has been examined under reaction conditions similar to those found in active phagosomes [25].

Associations of hypochlorous acid with other chemical compounds

• The ability of the triggered neutrophil to solubilize the matrix in the presence of alpha-1-proteinase inhibitor was unaffected by superoxide dismutase or hydroxyl radical scavengers but was markedly impaired by catalase, azide, or hypochlorous acid scavengers [11].
• Chloramine T, H2O2, or hypochlorous acid generated from H2O2 by myeloperoxidase rapidly destroy 75-90% of TM cofactor activity [26].
• Finally, the hydrogen peroxide scavenger catalase inhibited alpha MCCT lytic activity in vitro; however, the hypochlorous acid scavengers alanine, serine, and valine were without effect [27].
• Aldehyde production by purified myeloperoxidase required H202 and chloride, and was mimicked by reagent hypochlorous acid (HOCl) in the absence of enzyme, suggesting that the reaction pathway involves a chlorinated intermediate [28].
• The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport [29].

Gene context of hypochlorous acid

• Myeloperoxidase, a heme protein expressed by select populations of artery wall macrophages, initiates one potentially mutagenic pathway by generating hypochlorous acid [30].
• They ranged from 1.16 V at low hypochlorous acid to 1.09 V at higher hypochlorous acid for MPO and from 1.10 V to 1.03 V for EPO [31].
• CD64 signal transduction augmented superoxide anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production by PMNs of volunteers and group 1 [32].
• Hypochlorous acid stimulation of the mitogen-activated protein kinase pathway enhances cell survival [33].
• Both the release of chymase, a neutral protease, from mast cells and the oxidation of HDL by hypochlorous acid can impair the function of phospholipid transfer protein in reverse cholesterol transport [34].

Analytical, diagnostic and therapeutic context of hypochlorous acid

• To determine whether or not ingested bacteria were exposed to hypochlorous acid in neutrophil phagosomes, we labeled their proteins with [(13)C(6)]tyrosine and used gas chromatography with mass spectrometry to identify the corresponding chlorinated isotopes after the bacteria had been phagocytosed [35].
• These were characterized using fast atom bombardment-mass spectrometry and by chemical degradation using hypochlorous acid as well as transpeptidases [36].
• Therefore, one pathway for oxidative stress in hemodialysis patients appears to involve hypochlorous acid generated by the myeloperoxidase system of activated phagocytes [37].
• Bronchoalveolar lavage fluid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic inflammation, and 3-chlorotyrosine as a biomarker of the potent oxidant hypochlorous acid, which is formed by myeloperoxidase [38].
• Indeed, the increase in filtration pressures, produced by smoke, could be mimicked by the addition of the oxidant hypochlorous acid [39].

References