Neutrophil myeloperoxidase and its substrates: formation of specific markers and reactive compounds during inflammation

Abstract

Myeloperoxidase is an inflammatory enzyme that generates reactive hypochlorous acid in the presence of hydrogen peroxide and chloride ion. However, this enzyme also uses bromide ion or thiocyanate as a substrate to form hypobromous or hypothiocyanous acid, respectively. These species play important roles in host defense against the invasion of microorganisms. In contrast, these enzyme products modify biomolecules in hosts during excess inflammation, indicating that the action of myeloperoxidase is both beneficial and harmful. Myeloperoxidase uses other endogenous compounds, such as serotonin, urate, and l-tyrosine, as substrates. This broad-range specificity may have some biological implications. Target molecules of this enzyme and its products vary, including low-molecular weight thiols, proteins, nucleic acids, and lipids. The modified products represent biomarkers of myeloperoxidase action. Moderate inhibition of this enzyme might be critical for the prevention/modulation of excess, uncontrolled inflammatory events. Some phytochemicals inhibit myeloperoxidase, which might explain the reductive effect caused by the intake of vegetables and fruits on cardiovascular diseases.

Standardized Xylocarpus moluccensis fruit fraction mitigates collagen-induced arthritis in mice by regulating immune response

“…Previous report suggests that MPO level promotes oxidative stress through the production of hypochlorous acid and is found elevated in patients with active RA . Also, MPO is highly expressed in neutrophils . Therefore, the presence of elevated MPO activity in CIA mice and significant attenuation with F018 correlated well with the anti‐inflammatory effect of the extract.…”

Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

“…Thus, it is a widely studied enzyme in the fields of inflammation as well as oxidative stress and is often used as a biomarker for many diseases including atherosclerosis, rheumatoid arthritis, and neurodegenerative diseases [21]. The most common diseases linked with the MPO system are summarized in Table 2 and include the changes of the MPO concentration or activity, the investigated matrix, and finally the method by which the MPO amount and/or its activity was determined.…”

“…This is surprising, because Br − is about three orders of magnitude less abundant in comparison to Cl − (about 10 −1 versus 10 −4  M) and implies that bromide is preferentially metabolized by MPO. Furthermore, HOBr can be generated indirectly by the reaction between HOCl and bromide [39] which is also used to synthesize HOBr in the laboratory:$\begin{array}{c}T1{\mathrm{B}\mathrm{r}}^{-}+\mathrm{H}\mathrm{O}\mathrm{C}\mathrm{l}⟶\mathrm{H}\mathrm{O}\mathrm{B}\mathrm{r}+{\mathrm{C}\mathrm{l}}^{-}\end{array}$Both HOCl and HOBr are strongly oxidizing agents with the ability to modify amino moieties in proteins, DNA or PLs (such as PE and PS) resulting in the generation of chloramines and bromamines as primary products [21]. …”

Blood–brain barrier breakdown and myeloperoxidase activity in silver catfish experimentally infected with Pseudomonas aeruginosa

“…This enzyme performs an essential function by carrying out antimicrobial activity using HOCl to invade the bacterial pathogens (Tian, Ding, Peng, & Lu, ). However, excessive HOCl may oxidize host biomolecules during inflammation, inducing necrosis in the surrounding tissue through oxidative stress mediated by the release of large amounts of reactive oxygen species (ROS) and HOCl (Kato, ). In this sense, Miric et al.…”

“…This enzyme performs an essential function by carrying out antimicrobial activity using HOCl to invade the bacterial pathogens (Tian, Ding, Peng, & Lu, 2017). However, excessive HOCl may oxidize host biomolecules during inflammation, inducing necrosis in the surrounding tissue through oxidative stress mediated by the release of large amounts of reactive oxygen species (ROS) and HOCl (Kato, 2016). In this sense, Miric et al (2010) demonstrated that upregulation of cerebral MPO activity, through ROS generation, was associated with intense inflammatory and oxidative damage, contributing to BBB disruption and bacterial invasion of the CNS.…”