Abstract
The ether-lipid precursor sn-1-O-hexadecylglycerol (HG) can be used to compensate for early metabolic defects in ether-lipid biosynthesis. To investigate a possible metabolic link between ether-linked phospholipids and the rest of the cellular lipidome, we incubated HEp-2 cells with HG. Mass spectrometry analysis revealed major changes in the lipidome of HG-treated cells compared to that of untreated cells or cells treated with palmitin, a control substance for HG containing an acyl group instead of the ether group. We present quantitative data for a total of 154 species from 17 lipid classes. These species are those constituting more than 2% of their lipid class for most lipid classes, but more than 1% for the ether lipids and glycosphingolipids. In addition to the expected ability of HG to increase the levels of ether-linked glycerophospholipids with 16 carbon atoms in the sn-1 position, this precursor also decreased the amounts of glycosphingolipids and increased the amounts of ceramide, phosphatidylinositol and lysophosphatidylinositol. However, incubation with palmitin, the fatty acyl analogue of HG, also increased the amounts of ceramide and phosphatidylinositols. Thus, changes in these lipid classes were not ether lipid-dependent. No major effects were observed for the other lipid classes, and cellular functions such as growth and endocytosis were unaffected. The data presented clearly demonstrate the importance of performing detailed quantitative lipidomic studies to reveal how the metabolism of ether-linked glycerophospholipids is coupled to that of glycosphingolipids and ester-linked glycerophospholipids, especially phosphatidylinositols.
Highlights
Membrane lipid composition is critical for cell signaling, intracellular transport and cell proliferation
More than 300 species from 17 lipid classes were quantified following extraction of lipids from HEp-2 control cells as well as from cells treated with HG and palmitin
Similar data were obtained in an initial experiment with control cells and cells treated with HG
Summary
Membrane lipid composition is critical for cell signaling, intracellular transport and cell proliferation. Phosphatidylinositolphosphates (PIPs; abbreviations of lipid classes given in Methods under the heading Annotation of lipid species) are involved in recruiting a variety of cytosolic proteins involved in endocytosis and intracellular transport [2]. Knowledge about the role of single lipid species and the complex interplay between these lipids and proteins is crucial for our understanding of normal cell growth, as well as changes occurring in e.g. cancer cells. Alterations in lipid composition are associated with cancer, and there is evidence that the lipids in food, for instance the content of unsaturated fat, is important for the incidence of certain cancer types [4]. Attempts are being made to treat cancer with agents that modify lipid composition. Inhibiting lipid anchoring of kinases such as Ras might change cell growth [6]
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