Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 113, Issue -, Pages 395-405Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2017.10.344
Keywords
Selenium; Kinetics; Inflammation; Extracellular matrix; Protein oxidation
Funding
- Novo Nordisk Foundation [NNF13OC0004294, NNF15OC0018300]
- CNPq
- CAPES
- FAPERGS
- Novo Nordisk Fonden [NNF15OC0018300, NNF13OC0004294] Funding Source: researchfish
Ask authors/readers for more resources
Activated white blood cells generate multiple oxidants in response to invading pathogens. Thus, hypochlorous acid (HOCl) is generated via the reaction of myeloperoxidase (from neutrophils and monocytes) with hydrogen peroxide, and peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent is formed from superoxide radicals and nitric oxide, generated by stimulated macrophages. Excessive or misplaced production of these oxidants has been linked to multiple human pathologies, including cardiovascular disease. Atherosclerosis is characterized by chronic inflammation and the presence of oxidized materials, including extracellular matrix (ECM) proteins, within the artery wall. Here we investigated the potential of selenium-containing indoles to afford protection against these oxidants, by determining rate constants (k) for their reaction, and quantifying the extent of damage on isolated ECM proteins and ECM generated by human coronary artery endothelial cells (HCAECs). The novel selenocompounds examined react with HOCl with k 0.2-1.0 x 10(8) M-1 s(-1), and ONOOH with k 4.5-8.6 - x 10(5) M-1 s(-1). Reaction with H2O2 is considerably slower (k < 0.25 M-1 s(-1)). The seleno-compound 2-phenyl-3-(phenylselanyl) imidazo[1,2-alpha] pyridine provided protection to human serum albumin (HSA) against HOCl-mediated damage (as assessed by SDS-PAGE) and damage to isolated matrix proteins induced by ONOOH, with a concomitant decrease in the levels of the biomarker 3-nitrotyrosine. Structural damage and generation of 3-nitroTyr on HCAEC-ECM were also reduced. These data demonstrate that the novel selenium-containing compounds show high reactivity with oxidants and may modulate oxidative and nitrosative damage at sites of inflammation, contributing to a reduction in tissue dysfunction and atherogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available