On the Role of Paraoxonase-1, Chemokine (C-C motif) Ligand 2 and Metabolism in Oxidation, Inflammation and Disease. A 2021 Update

Abstract

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Usefulness of plasma and apolipoprotein B-depleted serum samples in paraoxonase 1 assessment

“…In addition to the suppression of LOOH accumulation, PON1 contributes to various HDL functions, such as inhibiting the release of in ammatory factors from macrophages [4] and promoting a cholesterol e ux via an ATPbinding cassette transporter A1 [5]. Thus, PON1 is also considered as a clinical parameter, and many studies have investigated associations of PON1 with a wide range of diseases, including atherosclerosis, cancer, and other infectious diseases [6][7][8][9].…”