Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 641, Issue -, Pages 31-38Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2018.01.010
Keywords
Chlorinated lipidome; Neutrophil activation; Plasmalogens; Inflammation
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Funding
- National Institutes of Health [R01GM115553]
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Myeloperoxidase produces the two-electron oxidant HOCl, which targets plasmalogen phospholipids liberating 2-chlorofatty aldehyde. 2-Chlorofatty aldehyde has four known fates: 1) oxidation to 2-chlorofatty acid; 2) reduction to 2-chlorofatty alcohol; 3) Schiff base adduct formation with proteins and amines; and 4) reactivity with glutathione through nucleophilic attack of the alpha-chlorinated carbon. 2-Chlorofatty acid does not undergo conventional fatty acid beta-oxidation due to the presence of the a alpha-chlorinated carbon; however, 2-chlorofatty acid does undergo sequential alpha-oxidation and beta-oxidation from the (omega-end, ultimately resulting in 2-chloroadipic acid urinary excretion. Recent studies have demonstrated that 2-chlorofatty acid clearance is increased by treatment with the PPAR-alpha agonist WY14643, which increases the enzymatic machinery responsible for hepatic omega-oxidation. Furthermore, 2-chlorofatty acid has been shown to be a PPAR-alpha agonist, and thus accelerates its own clearance. The roles of 2-chlorofatty aldehyde and 2-chlorofatty acid on leukocyte and endothelial function have been explored by several groups, suggesting that chlorinated lipids induce endothelial cell dysfunction, neutrophil chemotaxis, monocyte apoptosis, and alterations in vascular tone. Thus, the chlorinated lipidome, produced in response to leukocyte activation, is a potential biomarker and therapeutic target to modulate host response in inflammatory diseases.
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