Abstract
Oxidants are generated during many physiologic and pathological processes. Over-production is associated with host tissue damage, with this implicated in many human inflammatory diseases, including cardiovascular diseases, cystic fibrosis, asthma, kidney disease and degenerative neurological conditions. Unlike cells, the extracellular matrix (ECM) is poorly protected against oxidation, and evidence has been presented for significant ECM damage in atherosclerotic lesions. Activation of resident leukocytes results in O2•− and H2O2 formation and the release of myeloperoxidase (MPO). MPO catalyzes conversion of H2O2 and Cl− to the damaging oxidant HOCl, but it can also oxidize Br−, I−, SCN−, NO2− and organic substrates. Although the effects of HOCl are established, modifications induced by the mixture of anions present in plasma is poorly understood. We hypothesized that these ions might modulate the damage induced by HOCl. We have quantified chlorination and nitration damage to both isolated human plasma fibronectin and cell-derived ECM (from human coronary artery smooth muscle cells) induced by a MPO-H2O2 system in the presence of Cl−, Br−, I−, SCN− at physiological concentrations, and also with or without NO2−, via ELISA and LC-MS. Nitration levels increased with increasing amounts of NO2−, while the extent of HOCl-generated damage decreased, on both targets. These data indicate that NO2− can inhibit chlorination induced by MPO-H2O2-Cl−. The extent of chlorination was also decreased by other anions (and combinations of these), with SCN− inducing a marked decrease in the extent of damage. Overall, these data shown that both NO2− and SCN− can modulate damage induced by the MPO system. These studies with physiologically-relevant anion levels better mimic the in vivo situation, and also suggest that elevation of both NO2− and SCN−, which can be readily achieved in humans, may modulate the extent of damage induced at sites of inflammation, including within the artery wall during atherosclerosis development
Original language | English |
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Journal | Free Radical Biology and Medicine |
Volume | 177 |
Issue number | Suppl. 1 |
Pages (from-to) | 566 |
Number of pages | 1 |
ISSN | 0891-5849 |
DOIs | |
Publication status | Published - 2021 |
Event | Annual Meeting of the Society-for-Free-Radical-Research-Europe (SFRR-E) - Redox Biology in the 21st Century - A New Scientific Discipline - Belgrade, Serbia Duration: 15 Jun 2021 → 18 Jun 2021 |
Conference
Conference | Annual Meeting of the Society-for-Free-Radical-Research-Europe (SFRR-E) - Redox Biology in the 21st Century - A New Scientific Discipline |
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Country/Territory | Serbia |
City | Belgrade |
Period | 15/06/2021 → 18/06/2021 |