Abstract
Oxidized phospholipids (oxPLs) are components of oxidized LDL (oxLDL). It is known that oxLDL activates expression of a series of atherogenic genes and their oxPLs contribute to their biological activities. In this study we present the effects of 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on gene expression in RAW 264.7 macrophages using cDNA microarrays. PGPC affected the regulation of 146 genes, whereas POVPC showed only very minor effects. PGPC preferentially influenced expression of genes related to cell death, angiogenesis, cholesterol efflux, procoagulant mechanisms, atherogenesis, inflammation, and cell cycle. Many of these effects are known from studies with oxLDL or oxidized 1-hexadecanoyl-2-eicosatetra-5′,8′,11′,14′-enoyl-sn-glycero-3-phosphocholine (oxPAPC), containing PGPC in addition to other oxPL species. It is known that POVPC efficiently reacts with proteins by Schiff base formation, whereas PGPC only physically interacts with its biological targets. POVPC seems to affect cell physiology to a great extent on the protein level, whereas PGPC gives rise to both the modulation of protein function and regulation on the transcriptional level.
Highlights
OxPLs are components of oxidized LDL (oxLDL) which plays an important role in atherogenesis
DAVID GO analysis was performed to identify biological functions of genes that were regulated under the influence of present the effects of 1palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) showing that the response of the transcriptome to this lipid largely matches the effects of its parent oxLDL, which is a highly atherogenic particle
We found that the modified lipoprotein and the truncated oxidized phospholipids PGPC and POVPC induced apoptosis in cultured vascular smooth muscle cells and RAW macrophages
Summary
OxPLs are components of oxLDL which plays an important role in atherogenesis. This lipoprotein particle interacts with the cells of the arterial wall leading to cell-specific pathophysiological consequences. It has already been established that the truncated oxidized phospholipids PGPC and POVPC are toxic components of oxLDL and induce apoptosis in cultured macrophages and vascular smooth muscle cells [1], [2], [3]. Both compounds are generated from PAPC under oxidative stress and are structurally very similar. They contain a long fatty acyl chain and a short carboxylic acid residue in positions sn-1 and 22, respectively. It has been speculated that POVPC might preferentially interact with the cellular components on the protein level, whereas PGPC could undergo a great variety of physical interactions with proteins and other biomolecules, e.g. by modulating gene expression directly or indirectly via transcription factors
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