21 research outputs found
Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase
Platelet-activating factor (PAF) is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation
Circulating Platelet-Activating Factor Is Primarily Cleared by Transport, Not Intravascular Hydrolysis by Lipoprotein-Associated Phospholipase A 2
Platelet-activating factor acetylhydrolase in plasma lipoproteins from patients with ischemic stroke.
Platelet-activating factor acetylhydrolase in red cell membranes. Does decreased activity impair erythrocyte deformability in ischemic stroke patients?
PAF-acether-degrading acetylhydrolase in plasma LDL is inactivated by copper- and cell-mediated oxidation.
Relationship of molecular structure to the mechanism of lysophospholipid-induced smooth muscle cell proliferation
Effect of a cigarette smoke extract on the metabolism of the proinflammatory autacoid, platelet-activating factor.
Generation and Biological Activities of Oxidized Phospholipids
Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of âmodified-selfâ type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes current knowledge on the mechanisms of formation, structures, and biological activities of OxPLs. Furthermore, potential applications of OxPLs as disease biomarkers, as well as experimental therapies targeting OxPLs, are described, providing a broad overview of an emerging class of lipid mediators. Antioxid. Redox Signal. 12, 1009â1059