ascorbic-acid and hypobromous-acid

Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2'-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms.

Topics: Agaricales; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Bromates; Deoxyguanosine; DNA; Ergothioneine; Glutathione; Halogenation; Hypochlorous Acid; Inflammation; Male; Mice; Mice, Hairless; Peroxidase; Ultraviolet Rays

We describe the synthesis, properties, and application of two reversible fluorescent probes, mCy-TemOH and Cy-TemOH, for HOBr sensing and imaging in live cells. The two probes contain a hydroxylamine functional group for the monitoring of HOBr oxidation/ascorbic acid reduction events. Confocal fluorescence microscopy has established the HOBr detection in live-cells.

Topics: Animals; Ascorbic Acid; Bromates; Bromides; Cell Line; Cyclic N-Oxides; Eosinophil Peroxidase; Fluorescent Dyes; Hydrogen Peroxide; Hydroxylamines; Indoles; Macrophages; Mice; Microscopy, Confocal; Molecular Imaging; Oxidation-Reduction; Potassium Compounds; Spectrometry, Fluorescence

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, catalyzes the oxidation of halides to hypohalous acids. At plasma concentrations of halides, hypochlorous acid (HOCl) is the major strong oxidant produced. In contrast, the related enzyme eosinophil peroxidase preferentially generates hypobromous acid (HOBr). Since reagent and MPO-derived HOCl converts low-density lipoprotein (LDL) to a potentially atherogenic form, we investigated the effects of HOBr on LDL modification. Compared to HOCl, HOBr caused 2-3-fold greater oxidation of tryptophan and cysteine residues of the protein moiety (apoB) of LDL and 4-fold greater formation of fatty acid halohydrins from the lipids in LDL. In contrast, HOBr was 2-fold less reactive than HOCl with lysine residues and caused little formation of N-bromamines. Nevertheless, HOBr caused an equivalent increase in the relative electrophoretic mobility of LDL as HOCl, which was not reversed upon subsequent incubation with ascorbate, in contrast to the shift in mobility caused by HOCl. Similar apoB modifications were observed with HOBr generated by MPO/H(2)O(2)/Br(-). In the presence of equivalent concentrations of Cl(-) and Br(-), modifications of LDL by MPO resembled those seen in the presence of Br(-) alone. Interestingly, even at physiological concentrations of the two halides (100 mM Cl(-), 100 microM Br(-)), MPO utilized a portion of the Br(-) to oxidize apoB cysteine residues. MPO also utilized the pseudohalide thiocyanate to oxidize apoB cysteine residues. Our data show that even though HOBr has different reactivities than HOCl with apoB, it is able to alter the charge of LDL, converting it into a potentially atherogenic particle.

Topics: Apolipoproteins B; Ascorbic Acid; Bromates; Humans; Hydrogen Peroxide; Hypochlorous Acid; Leukocytes; Lipid Peroxidation; Lipoproteins, LDL