Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Xu, S; Chuang, CY; Malle, E; Gamon, LF; Hawkins, CL; Davies, MJ.
Influence of plasma halide, pseudohalide and nitrite ions on myeloperoxidase-mediated protein and extracellular matrix damage.
Free Radic Biol Med. 2022; 188:162-174 Doi: 10.1016/j.freeradbiomed.2022.06.222
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Malle Ernst

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

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 H₂O₂ to oxidize other substrates, and we hypothesized that mixtures of other plasma anions, including bromide (Br^-), iodide (I^-), thiocyanate (SCN^-) and nitrite (NO₂^-), at normal or supplemented concentrations, might modulate MPO-mediated HOCl damage. For the (pseudo)halide anions, only SCN^- significantly modulated HOCl formation (IC₅₀ ∼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. NO₂^- 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 NO₂^- concentrations (0.5-20 μM) diminished HOCl-mediated modification of tyrosine and methionine, whereas tryptophan loss was enhanced. At higher NO₂^- 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^- (but not Br^- or I^-) can modulate protein modification induced by MPO, including the extent of chlorination. In contrast, NO₂^- 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 NO₂^- levels are often elevated.

Find related publications in this database (Keywords)

Myeloperoxidase

Hypochlorous acid

Extracellular matrix

Nitrite

Thiocyanate

Fibronectin

Smooth muscle cells

Nitration

© Med Uni Graz • Imprint