Oxidatively modified fatty acyl chain determines physicochemical properties of aggregates of oxidized phospholipids

Abstract

In vivo oxidation of glycerophospholipid generates a variety of products including truncated oxidized phospholipids (tOx-PLs). The fatty acyl chains at the sn-2 position of tOx-PLs are shorter in length than the parent non-oxidized phospholipids and contain a polar functional group(s) at the end. The effect of oxidatively modified sn-2 fatty acyl chain on the physicochemical properties of tOx-PLs aggregates has not been addressed in detail, although there are few reports that modified fatty acyl chain primarily determines the biological activities of tOx-PLs. In this study we have compared the properties of four closely related tOx-PLs which differ only in the type of modified fatty acyl chain present at the sn-2 position: 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC), 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), and 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC). Aggregates of individual tOx-PL in aqueous solution were characterized by fluorescence spectroscopy, size exclusion chromatography, native polyacrylamide and agarose gel electrophoresis. The data suggest that aggregates of four closely related tOx-PLs form micelle-like particles of considerably different properties. Our result provides first direct evidence that because of the specific chemical composition of the sn-2 fatty acyl chain aggregates of particular tOx-PL possess a distinctive set of physicochemical properties.

Protein modification by aldehydophospholipids and its functional consequences

“…Probing membrane properties with a set of fluorophores provided evidence that the microenvironment sensed in POVPC aggregates is less polar and less hydrated than in artificial membranes containing PGPC [15]. The dipolar surface potential of POVPC is also lower than the corresponding value for PGPC [15].…”

Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2

“…In the present study, CHO cells and CHO/ LPLA2 cells in which LPLA2 was constitutively overexpressed were treated with 15 M PAzPC, a concentration that is lower than the critical micellar concentration of PAzPC (27). The enzymatic activities and protein levels of LPLA2 in those cells were confirmed by using DOPC/sulfatide/NAS liposomes was significantly inhibited in the presence of AMD, but the release of palmitic acid by LPLA2 was not significantly different in the presence or absence of AMD (Fig.…”

A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury

“…1palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC, Cayman), 1-palmitoyl-2-(5'oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC, Cayman), 1-palmitoyl-2arachidonoyl-sn-glycero-3-phosphocholine (PAPC, Sigma), oxPAPC (oxidized PAPC, Avanti) or 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC, Cayman) in ethanol were dried under nitrogen and then suspended in RPMI containing 0.1% FBS with vigorous vortexing, water bath sonication, and further vortexing. The lipids were then added to culture medium to stimulate primed or unprimed macrophages for h. We used phospholipid concentrations that were below their critical micellar concentrations, which are 54 μM, 68 μM, and 50 μM for PGPC, POVPC and LPC respectively, and similar to levels found in animal tissues (Bochkov et al, 2010;Fruhwirth and Hermetter, 2008;Mauerhofer et al, 2016;Pande et al, 2010). Brief incubation in 10% serum, used for many in vitro studies of oxPL activities, has been reported to convert POVPC and PGPC to LPC (Stemmer et al, 2012).…”