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Influence of plasma halide, pseudohalide and nitrite ions on myeloperoxidase-mediated protein and extracellular matrix damage.
- Source :
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Free radical biology & medicine [Free Radic Biol Med] 2022 Aug 01; Vol. 188, pp. 162-174. Date of Electronic Publication: 2022 Jun 16. - Publication Year :
- 2022
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Abstract
- Myeloperoxidase (MPO) mediates pathogen destruction by generating the bactericidal oxidant hypochlorous acid (HOCl). Formation of this oxidant is however associated with host tissue damage and disease. MPO also utilizes H <subscript>2</subscript> O <subscript>2</subscript> to oxidize other substrates, and we hypothesized that mixtures of other plasma anions, including bromide (Br <superscript>-</superscript> ), iodide (I <superscript>-</superscript> ), thiocyanate (SCN <superscript>-</superscript> ) and nitrite (NO <subscript>2</subscript> <superscript>-</superscript> ), at normal or supplemented concentrations, might modulate MPO-mediated HOCl damage. For the (pseudo)halide anions, only SCN <superscript>-</superscript> significantly modulated HOCl formation (IC <subscript>50</subscript> ∼33 μM), which is within the normal physiological range, as judged by damage to human plasma fibronectin or extracellular matrix preparations detected by ELISA and LC-MS. NO <subscript>2</subscript> <superscript>-</superscript> modulated HOCl-mediated damage, in a dose-dependent manner, at physiologically-attainable anion concentrations. However, this was accompanied by increased tyrosine and tryptophan nitration (detected by ELISA and LC-MS), and the overall extent of damage remained approximately constant. Increasing NO <subscript>2</subscript> <superscript>-</superscript> concentrations (0.5-20 μM) diminished HOCl-mediated modification of tyrosine and methionine, whereas tryptophan loss was enhanced. At higher NO <subscript>2</subscript> <superscript>-</superscript> concentrations, enhanced tyrosine and methionine loss was detected. These analytical data were confirmed in studies of cell adhesion and metabolic activity. Together, these data indicate that endogenous plasma levels of SCN <superscript>-</superscript> (but not Br <superscript>-</superscript> or I <superscript>-</superscript> ) can modulate protein modification induced by MPO, including the extent of chlorination. In contrast, NO <subscript>2</subscript> <superscript>-</superscript> alters the type of modification, but does not markedly decrease its extent, with chlorination replaced by nitration. These data also indicate that MPO could be a major source of nitration in vivo, and particularly at inflammatory sites where NO <subscript>2</subscript> <superscript>-</superscript> levels are often elevated.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 188
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 35718304
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2022.06.222