scholarly journals Fatty acid and phospholipid chlorohydrins cause cell stress and endothelial adhesion.

2006 ◽  
Vol 53 (4) ◽  
pp. 761-768 ◽  
Author(s):  
Gary Dever ◽  
Cherry L Wainwright ◽  
Simon Kennedy ◽  
Corinne M Spickett
Keyword(s):  
Fatty Acid ◽  
Biological Effects ◽  
Low Density Lipoprotein ◽  
Active Form ◽  
Density Lipoprotein ◽  
Oxidation Products ◽  
Low Density ◽  
Dependent Manner ◽  
Phagocytic Cells ◽  
Arachidonic Acids

The oxidation of low-density lipoprotein (LDL) is thought to contribute to atherogenesis, which is an inflammatory disease involving activation of phagocytic cells. Myeloperoxidase, an enzyme which is able to produce hypochlorous acid (HOCl), is released from these phagocytic cells, and has been found in an active form in atherosclerotic plaques. HOCl can oxidize both the lipid and protein moiety of LDL, and HOCl-modified LDL has been found to be pro-inflammatory, although it is not known which component is responsible for this effect. As HOCl can oxidize lipids to give chlorohydrins, we hypothesized that phospholipid chlorohydrins might have toxic and pro-inflammatory effects. We have formed chlorohydrins from fatty acids (oleic, linoleic and arachidonic acids) and from phospholipids (stearoyl-oleoyl phosphatidylcholine, stearoyl-linoleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine), and investigated various biological effects of these oxidation products. Fatty acid and phospholipid chlorohydrins were found to deplete ATP levels in U937 cells in a concentration-dependent manner, with significant effects observed at concentrations of 25 microM and above. Low concentrations (25 microM) of stearoyl-oleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine chlorohydrins were also found to increase caspase-3 activity. Finally, stearoyl-oleoyl phosphatidylcholine chlorohydrin increased leukocyte adhesion to artery segments isolated from C57Bl/6 mice. These results demonstrate potentially harmful effects of lipid chlorohydrins, and suggest that they may contribute to some of the pro-inflammatory effects that HOCl-modified low density lipoprotein has been found to induce.

scholarly journals Changes in fatty acid compositions of total serum and lipoprotein particles, in growing rats given protein-deficient diets with either hydrogenated coconut or salmon oils as fat sources

1994 ◽  
Vol 71 (3) ◽  
pp. 375-387 ◽  
Author(s):  
Mahmoud Bouziane ◽  
Josiane Prost ◽  
Jacques Belleville
Keyword(s):  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coconut Oil ◽  
Protein Malnutrition ◽  
Total Serum ◽  
Low Density ◽  
Apo B ◽  
Growing Rats ◽  
Arachidonic Acids

The present study examines the effects of dietary saturated (hydrogenated coconut oil) and polyunsaturated (salmon oil) fats on the composition and metabolism of lipoproteins in growing rats fed on protein-deficient diets. Four groups of rats were fed on the following diets for 28 d: 200 g casein+50 g coconut oil (COC)/kg, 20 g casein+50 g coconut oil (COd)/kg, 200 g casein + 50 g salmon oil (SAC)/kg, 20 g casein+50 g salmon oil (SAd)/kg. Both protein-deficient groups exhibited low concentrations of protein and triacylglycerol (in serum, very-low-density lipoprotein (VLDL), low-density lipoprotein-high-density lipoprotein, (LDL-HDL1) and HDL2-3), of cholesterol (in LDL-HDL1) and of phospholipids (in VLDL). Furthermore, serum and VLDL cholesterol concentrations were also reduced in the SAd group. Compared with rats given 200 g casein/kg diets, those fed on low-protein diets presented lower linoleic and arachidonic acid levels, in serum phospholipids and a dramatic decrease in the polyunsaturated: saturated fatty acid value. Relative amounts of linoleic and arachidonic acids in phospholipids of VLDL and HDL2-3 were also lowered in the Cod group but not in the SAd group. However, proportions of 22:5n-6 and 22:6n-3 in VLDL and HDL2-3 phospholipid fractions were enhanced in the Cod and SAd groups respectively. The most affected apolipoproteins (apo) were apo B100 and apo B48 in rats fed on protein-deficient diets, apo A1 and apo E in the Cod group, and apo AIV, in the SAd group. Compared with rats fed hydrogenated coconut oil diets, those fed salmon oil diets had enhanced LDL-HDL1 and HDL2-3 but lower VLDL total apolipoproteins (mainly due to a fall in apo B100, and apo B48). Arachidonic and eicosapentaenoic acids, which are impaired by protein deficiency, are the precursors of prostaglandins, thromboxanes and leukotrienes which are implicated in a number of regulatory processes. Our results demonstrate that protein malnutrition is associated with impaired metabolism of arachidonic and eicosapentaenoic acids. Protein malnutrition and essential fatty acid (EFA) deficiency are characterized by many common clinical features and the Link between the two may be an impaired production of eicosanoids, since arachidonic and eicosapentaenoic acids are the precursors of these important metabolic regulators. Because of the apparent involvement of EFA deficiency in the aetiology of protein malnutrition, it may he prudent to include adequate amounts of EFA in diets of infants suffering from kwashiorkor.

scholarly journals The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bushra Yusuf ◽  
Ilya Mukovozov ◽  
Sajedabanu Patel ◽  
Yi-Wei Huang ◽  
Guang Ying Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Super Resolution ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Cortical Actin ◽  
Cytoskeletal Remodeling ◽  
Atherosclerotic Lesions ◽  
Modified Lipoproteins

AbstractAtherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.

scholarly journals Low-density-lipoprotein-receptor-related protein (LRP) interacts with a GTP-binding protein

1998 ◽  
Vol 336 (2) ◽  
pp. 381-386 ◽  
Author(s):  
Lothar GORETZKI ◽  
Barbara M. MUELLER
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Dependent Manner ◽  
Related Protein ◽  
Gtp Binding ◽  
Density Lipoprotein Receptor ◽  
Dose Dependent ◽  
Lipoprotein Receptor Related Protein

The low-density-lipoprotein-receptor-related protein (LRP) binds and internalizes numerous ligands, including lipoproteins, proteinase–inhibitor complexes and others. We have shown previously that LRP-mediated ligand internalization is dependent on cAMP-dependent protein kinase (PKA) activity. Here, we investigated whether ligation of LRP increases the intracellular cAMP level and PKA activity via a stimulatory GTP-binding protein. Treatment of LRP-expressing cell lines with the LRP ligands lactoferrin or urokinase-type plasminogen activator caused a significant elevation in cAMP and stimulated PKA activity in a dose-dependent manner. Addition of the 39 kDa receptor-associated protein (RAP), an antagonist for ligand interactions with LRP, blocked the lactoferrin-induced increase in PKA activity, demonstrating a requirement for ligand binding to LRP. Incubation of cell membrane fractions with lactoferrin increased GTPase activity in a time- and dose-dependent manner, and treatment with LRP ligands suppressed cholera-toxin-mediated ADP-ribosylation of the Gsα subunit of a heterotrimeric G-protein. Affinity precipitation of LRP with RAP resulted in co-precipitation of two isoforms of Gsα from detergent extracts. We thus conclude that LRP is a signalling receptor that associates directly with a stimulatory heterotrimeric G-protein and activates a downstream PKA-dependent pathway.

scholarly journals Very-Low-Density Lipoprotein Receptor Fragment Shed from HeLa Cells Inhibits Human Rhinovirus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 10246-10250 ◽  
Author(s):  
Thomas C. Marlovits ◽  
Christina Abrahamsberg ◽  
Dieter Blaas
Keyword(s):  
Hela Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intercellular Adhesion Molecule ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Dependent Manner ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

ABSTRACT The large family of human rhinoviruses, the main causative agents of the common cold, is divided into the major and the minor group based on receptor specificity. Major group viruses attach to intercellular adhesion molecule 1 (ICAM-1), a member of the immunoglobulin superfamily, whereas minor group viruses use low-density lipoprotein receptors (LDLR) for cell entry. During early attempts aimed at isolating the minor group receptor, we discovered that a protein with virus binding activity was released from HeLa cells upon incubation with buffer at 37°C (F. Hofer, B. Berger, M. Gruenberger, H. Machat, R. Dernick, U. Tessmer, E. Kuechler, and D. Blaas, J. Gen. Virol. 73:627–632, 1992). In light of the recent discovery of several new members of the LDLR family, we reinvestigated the nature of this protein and present evidence for its being derived from the human very-low density lipoprotein receptor (VLDLR). A soluble VLDLR fragment encompassing the eight complement type repeats and representing the N-terminal part of the receptor was then expressed in the baculovirus system; both the shed protein and the recombinant soluble VLDLR bind minor group viruses and inhibit viral infection of HeLa cells in a concentration-dependent manner.

scholarly journals The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

scholarly journals A Prospective Study of Trans Fatty Acids in Erythrocytes and Risk of Coronary Heart Disease

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1858-1865 ◽  
Author(s):  
Qi Sun ◽  
Jing Ma ◽  
Hannia Campos ◽  
Susan E. Hankinson ◽  
JoAnn E. Manson ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Fatty Acid ◽  
Acid Content ◽  
Low Density Lipoprotein ◽  
Fatty Acid Content ◽  
Density Lipoprotein ◽  
Elevated Risk ◽  
Low Density ◽  
Relative Risks

Background— High consumption of trans fat has been linked to the risk of coronary heart disease (CHD). We assessed the hypothesis that higher trans fatty acid contents in erythrocytes were associated with an elevated risk of CHD in a nested case-control study among US women. Methods and Results— Blood samples were collected from 32 826 participants of the Nurses’ Health Study from 1989 to 1990. During 6 years of follow-up, 166 incident cases of CHD were ascertained and matched with 327 controls. Total trans fatty acid content in erythrocytes was significantly correlated with dietary intake of trans fat (correlation coefficient=0.44, P <0.01) and was associated with increased plasma low-density lipoprotein cholesterol ( P for trend =0.06), decreased plasma high-density lipoprotein cholesterol concentrations ( P for trend <0.01), and increased plasma low-density lipoprotein to high-density lipoprotein ratio ( P for trend <0.01). After adjustment for age, smoking status, and other dietary and lifestyle cardiovascular risk factors, higher total trans fatty acid content in erythrocytes was associated with an elevated risk of CHD. The multivariable relative risks (95% confidence intervals) of CHD from the lowest to highest quartiles of total trans fatty acid content in erythrocytes were 1.0 (reference), 1.6 (0.7 to 3.6), 1.6 (0.7 to 3.4), and 3.3 (1.5 to 7.2) ( P for trend <0.01). The corresponding relative risks were 1.0, 1.1, 1.3, and 3.1 ( P for trend <0.01) for a total of 18:1 trans isomers and 1.0, 1.5, 2.5, and 2.8 ( P for trend <0.01) for a total of 18:2 trans isomers. Conclusions— These biomarker data provide further evidence that high trans fat consumption remains a significant risk factor for CHD after adjustment for covariates.

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