Low doses (0.143 pg/ml per 1cP cells) of the lipopolysaccharide toxin (LPS) from Sulmonellu typhimurium were shown to increase (after an 18 h incubation) the intracellular content of free cholesterol (CH), esterified cholesterol (EC) and triglycerides (TG) by 3040% in the primary culture of rabbit hepatocytes. A similar increase was found for the incorporation of r4C]acetate into these lipids. The concentration of lipids in cultural medium, under these conditions, was also augmented: by 30-40s for CH; by 5&60% for TG and by 6&80% for EC. Higher doses (up to 50 ,ug/ml) of LPS hardly affected the lipid content in hepatocytes but strongly (by two-fold) inhibited the secretion of lipids. It is suggested that in vivo low concentrations of LPS in bloodstream (in the absence of conspicuous pathology) might induce hyperlipidemia directly influencing on hepatic cells, while, under the higher concentrations of LPS, hyperlipidemia caused by cachectin (or tumor necrosis factor) is probably observed.Lipopolysaccharide toxin; Hyperlipidemia; (Rabbit hepatocyte)
The composition, structure and localization of neutral glycosphingolipids of human aorta taken from subjects who had died after myocardial infarction were studied. Individual glycosphingolipids were purified by highperformance liquid chromatography and were characterized on the basis of their chromatographic mobility, carbohydrate composition, methylation analysis and by H-NMR spectroscopy. The main aortic glycosphingolipids were identified as glucosylceramide, lactosylceramide, globotriaosylceramide and globotetraosylceramide. Significant differences in the neutral glycosphingolipid composition of intima and media were detected.The neutral glycosphingolipid profile of medial plaques resembled that of unaffected media; however, significant differences were detected between intimal plaques and unaffected intima. Whereas the latter contained trihexosylceramide and globoside as the only neutral glycolipids, the intimal plaque glycolipids consisted mainly of glucosylceramide and also contained appreciable amounts of lactosylceramide which were completely absent in the unaffected intima. In comparison to intimal plaques, unaffected intima is characterized by a much higher content of cerebrosides terminating by B-galactosyl residues which are known to interact with growth factors and other external stimuli.It thus seems possible that the proliferative activity of smooth muscle cells in atherosclerotic diseases is to some extent associated with their neutral glycolipid profile.Neutral glycosphingolipids are known to be cell antigens and blood group substances [l]. Cell transformation leads to appearance of new glycolipid antigens [2]. During development of atherosclerosis, vessel tissues undergo dramatic changes 131 which eventually are also accompanied by the appearance of new glycolipid antigens. Previously we found the composition of acidic glycosphingolipids (gangliosides) in adult human aorta to change significantly during formation of atherosclerotic plaques [4] and that intimal gangliosides may participate in platelet adhesion to the vessel wall [23]. However up to now nothing was known about the composition and localization of neutral glycolipids in human aorta. In this paper we present rcsults of a detailed study of the neutral glycolipids of whole adult human aorta, intima, atherosclerotic plaques and underlying media.
MATERIALS AND METHODS
TissuesHuman thoratic aortas from 40 -60-year-old men and women who had died of myocardial infarction were obtained at autopsy within 1.5 -3 h after sudden death.Whole aorta samples (media plus intima) for investigating neutral glycolipid structures were received after adventitia, together with one third of the outer media, had been stripped away. Grossly normal areas and uncomplicated atherosclerotic plaques were cut out. The inner intima was separated from media mechanically along the secondary internal limiting membrane as described earlier [5, 61.
Extraction and purijication of neutral glycolipidsLipid extraction from whole aorta, alkaline treatment and dialysis were ...
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