| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Sphingomyelin and cholesterol promote HIV-1 gp41 pretransmembrane sequence surface aggregation and membrane restructuring Saez-Cirion, A., S. Nir, et al. (2002), J Biol Chem 277(24): 21776-85. Abstract: The interfacial sequence DKWASLWNWFNITNWLWYIK, preceding the transmembrane anchor of gp41 glycoprotein subunit, has been shown to be essential for fusion activity and incorporation into virions. HIV(c), a peptide representing this region, formed lytic pores in liposomes composed of the main lipids occurring in the human immunodeficiency virus, type 1 (HIV-1), envelope, i.e. 1-palmitoyl-2-oleoylphosphatidylcholine (POPC):sphingomyelin (SPM):cholesterol (Chol) (1:1:1 mole ratio), at low (>1:10,000) peptide-to-lipid mole ratio, and promoted the mixing of vesicular lipids at >1:1000 peptide-to-lipid mole ratios. Inclusion of SPM or Chol in POPC membranes had different effects. Whereas SPM sustained pore formation, Chol promoted fusion activity. Even if partitioning into membranes was not affected in the absence of both SPM and Chol, HIV(c) had virtually no effect on POPC vesicles. Conditions described to disturb occurrence of lateral separation of phases in these systems reproduced the high peptide-dose requirements for leakage as found in pure POPC vesicles and inhibited fusion. Surface aggregation assays using rhodamine-labeled peptides demonstrated that SPM and Chol promoted HIV(c) self-aggregation in membranes. Employing head-group fluorescent phospholipid analogs in planar supported lipid layers, we were able to discern HIV(c) clusters associated to ordered domains. Our results support the notion that the pretransmembrane sequence may participate in the clustering of gp41 monomers within the HIV-1 envelope, and in bilayer architecture destabilization at the loci of fusion. |
| Sphingomyelin and cholesterol: from membrane biophysics and rafts to potential medical applications Barenholz, Y. (2004), Subcell Biochem 37: 167-215. Abstract: The preferential sphingomyelin-cholesterol interaction which results from the structure and the molecular properties of these two lipids seems to be the physicochemical basis for the formation and maintenance of cholesterol/sphingolipid-enriched nano- and micro-domains (referred to as membrane "rafts") in the plane of plasma and other organelle (i.e., Golgi) membranes. This claim is supported by much experimental evidence and also by theoretical considerations. However, although there is a large volume of information about these rafts regarding their lipid and protein composition, their size, and their dynamics, there is still much to be clarified on these issues, as well as on how rafts are formed and maintained. It is well accepted now that the lipid phase of the rafts is the liquid ordered (LO) phase. However, other (non-raft) parts of the membrane may also be in the LO phase. There are indications that the raft LO phase domains are more tightly packed than the non-raft LO phase, possibly due to intermolecular hydrogen bonding involving sphingolipid and cholesterol. This also explains why the former are detergent-resistant membranes (DRM), while the non-raft LO phase domains are detergent-soluble (sensitive) membranes (DSM). Recent findings suggest that protein-protein interactions such as cross-linking can be controlled by protein distribution between raft and non-raft domains, and, as well, these interactions affect raft size distribution. The cholesterol/sphingomyelin-enriched rafts seem to be involved in many biological processes, mediated by various receptors, as exemplified by various lipidated glycosylphosphatidylinositol (GPI)- and acyl chain-anchored proteins that reside in the rafts. The rafts serve as signaling platforms in the cell. Various pathogens (viruses and toxins) utilize the raft domains on the host cell membrane as a port of entry, site of assembly (viruses), and port of exit (viral budding). Existence and maintenance of cholesterol-sphingomyelin rafts are dependent on the level of membrane cholesterol and sphingomyelin. This explains why reduction of cholesterol level--either through reverse cholesterol transport, using cholesterol acceptors such as beta-cyclodextrin, or through cholesterol biosynthesis inhibition using statins--interferes with many processes which involve rafts and can be applied to treating raft-related infections and diseases. Detailed elucidation of raft structure and function will improve understanding of biological membrane composition-structure-function relationships and also may serve as a new avenue for the development of novel treatments for major diseases, including viral infections, neurodegenerative diseases (Alzheimer's), atherosclerosis, and tumors. |
| Sphingomyelin biosynthesis and efflux correlates with cholesterol metabolism and is higher in vascular endothelial cells than in smooth muscle cells Greemland, M. and N. Savion (1993), Eur Heart J 14(5): 687-91. Abstract: We compared the metabolism of cellular phospholipids in bovine aortic endothelial and smooth muscle cells in culture. 3HCholine was incorporated in both cell types into phosphatidylcholine (86-90%) and sphingomyelin (10-14%). Endothelial cells demonstrated preferential efflux of sphingomyelin which represented 22.5% of the radiolabelled phospholipids in the incubation medium while in smooth muscle cells it represented 10%, so that after 7 days, the sphingomyelin in the medium represented 40% and 16% of total synthesized sphingomyelin in endothelial and smooth muscle cells, respectively. Incorporation of 3Hcholine by endothelial and smooth muscle cells was reduced in the presence of serum, but not in the presence of lipoprotein deficient serum, indicating that cells can acquire phosphatidylcholine and sphingomyelin from lipoproteins. Lipoproteins were shown also to support the efflux of cellular radiolabelled phospholipids from both cell types, but at a higher degree from endothelial cells than from smooth muscle cells. Exposure of these cultures to cholesterol rich serum increased the synthesis of phosphatidylcholine, and to a higher extent of sphingomyelin, with concomitant decrease in the efflux of these two phospholipids. These results demonstrate the role of cholesterol in the regulation of phosphatidylcholine and sphingomyelin biosynthesis and efflux in vascular cells. Furthermore, the higher efflux of sphingomyelin in endothelial cells than in smooth muscle cells may support the extensive efflux of cholesterol observed in endothelial cells and indicate biochemical differences in lipid metabolism between vascular endothelial and smooth muscle cells. |
| Sphingomyelin content of intestinal cell membranes regulates cholesterol absorption. Evidence for pancreatic and intestinal cell sphingomyelinase activity Chen, H., E. Born, et al. (1992), Biochem J 286 (Pt 3): 771-7. Abstract: Micellar cholesterol uptake and secretion were investigated in the human intestinal cell line CaCo-2 following depletion of apical membrane sphingomyelin. The addition of exogenous sphingomyelinase, which hydrolysed 60% of prelabelled sphingomyelin, resulted in a 50% decrease in the uptake of cholesterol from bile salt micelles. The flux of membrane cholesterol into the cell by the hydrolysis of membrane sphingomyelin decreased the rate of cholesterol synthesis by 43% and inhibited hydroxymethylglutaryl-CoA reductase activity by 54%. Moreover, the rate of cholesterol esterification was increased 4-fold. Total cellular cholesterol mass was unchanged by the addition of sphingomyelinase; however, cholesteryl esters increased by 50% and the amount of unesterified cholesterol decreased significantly. The basolateral secretion of cholesterol mass was also decreased following sphingomyelin hydrolysis. Human pancreatic juice was found to contain neutral sphingomyelinase activity which required taurocholate for full expression. The presence of neutral sphingomyelinase activity was also documented in membranes prepared from CaCo-2 cells and in whole homogenates from human duodenal biopsies. The data suggest that the amount of sphingomyelin present in the apical membrane of the intestinal absorptive cell regulates cholesterol uptake from bile salt micelles. Sphingomyelinase activity within intestinal cells and in pancreatic juice could alter the sphingomyelin content of brush-border membranes of small intestinal absorptive cells and thus regulate the amount of cholesterol absorbed by the gut. |
| Sphingomyelin is much more effective than saturated phosphatidylcholine in excluding unsaturated phosphatidylcholine from domains formed with cholesterol van Duyl, B. Y., D. Ganchev, et al. (2003), FEBS Lett 547(1-3): 101-6. Abstract: In this study, we compared domain formation in raft-like mixtures of cholesterol and dioleoylphosphatidylcholine (DOPC) with either sphingomyelin (SM) or dipalmitoylphosphatidylcholine (DPPC). Using 2H nuclear magnetic resonance, we studied the properties of the lipid enriched in the fluid phase, DOPC. We found that acyl chain 2H-labeled DOPC is much less ordered in SM-containing mixtures than in those containing DPPC, suggesting that DOPC in the SM-containing mixture senses a lower concentration of cholesterol in its direct environment. Atomic force microscopy experiments demonstrated large differences in the size and shape of domains in the different mixtures. We propose that these various differences are a consequence of the preferential interaction of cholesterol for sphingolipids over glycerophospholipids. |
| Sphingomyelin/cholesterol ratio: an important determinant of glucose transport mediated by GLUT-1 in 3T3-L1 preadipocytes Al-Makdissy, N., M. Younsi, et al. (2003), Cell Signal 15(11): 1019-30. Abstract: Sphingomyelin pathway has been linked with insulin signaling through insulin-dependent GLUT-4 glucose transporter, but a relationship between sphingomyelin and the GLUT-1 transporter responsible for the basal (insulin-independent) glucose transport has not been clearly established. As GLUT-1 is mainly distributed to the cell surface, we explored the effects of changes in membrane sphingomyelin content on glucose transport through GLUT-1. The addition of exogenous sphingomyelin or glutathione (an inhibitor of endogenous sphingomyelinase) to the culture medium increased membrane sphingomyelin and cholesterol contents. Basal glucose uptake was enhanced and positively correlated to sphingomyelin (SM), cholesterol (CL) and SM/CL ratio. The exposure of 3T3-L1 preadipocytes to sphingomyelinase (SMase) significantly increased basal glucose uptake, membrane fluidity and decreased membrane sphingomyelin and cholesterol contents 60 min after SMase addition. There was no significant change in the abundance of GLUT-1 at the cell surface. The membrane sphingomyelin and cholesterol contents, fluidity and basal glucose transport returned to baseline levels within 2 h. The basal glucose uptake was negatively correlated with cholesterol contents and positively with SM/CL ratio. The SM/CL ratio might represent an important parameter controlling basal glucose uptake and a mechanism by which insulin resistance might be induced. |
| Sphingomyelin/phosphatidylcholine/cholesterol phase diagram: boundaries and composition of lipid rafts de Almeida, R. F., A. Fedorov, et al. (2003), Biophys J 85(4): 2406-16. Abstract: The ternary system palmitoylsphingomyelin (PSM)/palmitoyloleoylphosphatidylcholine (POPC)/cholesterol is used to model lipid rafts. The phase behavior of the three binary systems PSM/POPC, PSM/cholesterol, and POPC/cholesterol is first experimentally determined. Phase coexistence boundaries are then determined for ternary mixtures at room temperature (23 degrees C) and the ternary phase diagram at that temperature is obtained. From the diagram at 23 degrees C and the binary phase diagrams, a reasonable expectation is drawn for the ternary phase diagram at 37 degrees C. Several photophysical methodologies are employed that do not involve detergent extraction, in addition to literature data (e.g., differential scanning calorimetry) and thermodynamic rules. For the ternary phase diagrams, some tie-lines are calculated, including the one that contains the PSM/POPC/ cholesterol 1:1:1 mixture, which is often used in model raft studies. The diagrams here described are used to rationalize literature results, some of them apparently discrepant, and to discuss lipid rafts within the framework of liquid-ordered/liquid-disordered phase coexistence. |
| Sphingomyelinase activates GLUT4 translocation via a cholesterol-dependent mechanism Liu, P., B. J. Leffler, et al. (2004), Am J Physiol Cell Physiol 286(2): C317-29. Abstract: A basis for the insulin mimetic effect of sphingomyelinase on glucose transporter isoform GLUT4 translocation remains unclear. Because sphingomyelin serves as a major determinant of plasma membrane cholesterol and a relationship between plasma membrane cholesterol and GLUT4 levels has recently become apparent, we assessed whether GLUT4 translocation induced by sphingomyelinase resulted from changes in membrane cholesterol content. Exposure of 3T3-L1 adipocytes to sphingomyelinase resulted in a time-dependent loss of sphingomyelin from the plasma membrane and a concomitant time-dependent accumulation of plasma membrane GLUT4. Degradation products of sphingomyelin did not mimic this stimulatory action. Plasma membrane cholesterol amount was diminished in cells exposed to sphingomyelinase. Restoration of membrane cholesterol blocked the stimulatory effect of sphingomyelinase. Increasing concentrations of methyl-beta-cyclodextrin, which resulted in a dose-dependent reversible decrease in membrane cholesterol, led to a dose-dependent reversible increase in GLUT4 incorporation into the plasma membrane. Although increased plasma membrane GLUT4 content by cholesterol extraction with concentrations of methyl-beta-cyclodextrin above 5 mM most likely reflected decreased GLUT4 endocytosis, translocation stimulated by sphingomyelinase or concentrations of methyl-beta-cyclodextrin below 2.5 mM occurred without any visible changes in the endocytic retrieval of GLUT4. Furthermore, moderate loss of cholesterol induced by sphingomyelinase or low concentrations of methyl-beta-cyclodextrin did not alter membrane integrity or increase the abundance of other plasma membrane proteins such as the GLUT1 glucose transporter or the transferrin receptor. Regulation of GLUT4 translocation by moderate cholesterol loss did not involve known insulin-signaling proteins. These data reveal that sphingomyelinase enhances GLUT4 exocytosis via a novel cholesterol-dependent mechanism. |
| Sphingomyelinase D, a novel probe for cellular sphingomyelin: effects on cholesterol homeostasis in human skin fibroblasts Subbaiah, P. V., S. J. Billington, et al. (2003), J Lipid Res 44(8): 1574-80. Abstract: Sphingomyelin (SM) and free cholesterol (FC) are concentrated in the plasma membranes of eukaryotes; however, the physiological significance of their association is unclear. A common tool for studying the role of membrane SM is digestion with bacterial sphingomyelinase (SMase) C, which hydrolyzes SM to ceramide. However, it is not known whether the observed effects of SMase C treatment are due to the loss of SM per se or to the signaling effects of ceramide. In this study, we tested SMase D from Corynebacterium pseudotuberculosis, which hydrolyzes SM to ceramide phosphate, as an alternative probe. This enzyme specifically hydrolyzed SM in fibroblasts without causing accumulation of ceramide. Treatment of fibroblasts with SMase D stimulated translocation of PM FC to intracellular sites by <20% of the rate observed after SMase C digestion. The cells regenerated SM nearly completely within 5 h after SMase C treatment. However, even after 20 h, no regeneration occurred following SMase D digestion. These findings suggest that the translocation of PM FC caused by SMase C digestion is due to the cellular effects of ceramide rather than the loss of SM. Since ceramide phosphate does not appear to have such effects, we suggest that SMase D is a useful probe of membrane SM. |
| Sphingomyelin-cholesterol domains in phospholipid membranes: atomistic simulation Pandit, S. A., S. Vasudevan, et al. (2004), Biophys J 87(2): 1092-100. Abstract: We have carried out an atomic-level molecular dynamics simulation of a system of nanoscopic size containing a domain of 18:0 sphingomyelin and cholesterol embedded in a fully hydrated dioleylposphatidylcholine (DOPC) bilayer. To analyze the interaction between the domain and the surrounding phospholipid, we calculate order parameters and area per molecule as a function of molecule type and proximity to the domain. We propose an algorithm based on Voronoi tessellation for the calculation of the area per molecule of various constituents in this ternary mixture. The calculated areas per sphingomyelin and cholesterol are in agreement with previous simulations. The simulation reveals that the presence of the liquid-ordered domain changes the packing properties of DOPC bilayer at a distance as large as approximately 8 nm. We calculate electron density profiles and also calculate the difference in the thickness between the domain and the surrounding DOPC bilayer. The calculated difference in thickness is consistent with data obtained in atomic force microscopy experiments. |
| Sphingomyelin-cholesterol interactions in biological and model membranes Slotte, J. P. (1999), Chem Phys Lipids 102(1-2): 13-27. Abstract: Cholesterol and sphingomyelin are both important plasma membrane constituents in cells. It is now becoming evident that these two lipid classes affect each other's metabolism in the cell to an extent that was not previously appreciated. It is the aim of this review to present recent data in the literature concerning both molecular and membrane properties of the two lipid classes, how they interact in membranes (both biological and model), and the consequences their mutual interaction have on different functional and metabolic processes in cells and lipoproteins. |
| Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models Webb, M. S., T. O. Harasym, et al. (1995), Br J Cancer 72(4): 896-904. Abstract: This study reports on the development of a liposomal formulation of vincristine with significantly enhanced stability and biological properties. The in vitro and in vivo pharmacokinetic, tumour delivery and efficacy properties of liposomal vincristine formulations based on sphingomyelin (SM) and cholesterol were compared with liposomes composed of distearoylphosphatidylcholine (DSPC) and cholesterol. SM/cholesterol liposomes had significantly greater in vitro stability than did similar DSPC/cholesterol liposomes. SM/cholesterol liposomes also had significantly improved biological properties compared with DSPC/cholesterol. Specifically, SM/cholesterol liposomes administered intravenously retained 25% of the entrapped vincristine after 72 h in the circulation, compared with 5% retention in DSPC/cholesterol liposomes. The improved retention properties of SM/cholesterol liposomes resulted in plasma vincristine levels 7-fold higher than in DSPC/cholesterol liposomes. The improved circulation lifetime of vincristine in SM/cholesterol liposomes correlated with increased vincristine accumulation in peritoneal ascitic murine P388 tumours and in subcutaneous solid A431 human xenograft tumours. Increased vincristine delivery to tumours was also accompanied by increased anti-tumour efficacy. Treatment with SM/cholesterol liposomal formulations of vincristine resulted in greater than 50% cures in mice bearing ascitic P388 tumours, an activity that could not be achieved with the DSPC/cholesterol formulation. Similarly, treatment of mice with severe combined immunodeficiency (SCID) bearing solid human A431 xenograft tumours with SM/cholesterol vincristine formulations delayed the time required for 100% increase in tumour mass to > 40 days, compared with 5 days, 7 days and 14 days for mice receiving no treatment or treatment with free vincristine or DSPC/cholesterol formulations of vincristine respectively. |
| Sphingomyelin-metabolizing enzymes and protein kinase C activity in liver plasma membranes of rats fed with cholesterol-supplemented diet Nikolova-Karakashian, M. N., N. J. Gavrilova, et al. (1992), Biochem Cell Biol 70(7): 613-6. Abstract: The effect of cholesterol-supplemented diet on the activities of rat liver plasma membrane sphingomyelin-metabolizing enzymes and protein kinase C was studied. Protein kinase C, phosphatidylcholine:ceramide-phosphocholine transferase, and phosphatidylethanolamine:ceramide-phosphoethanolamine transferase activities were found to increase continuously and almost in parallel during the experimental period on cholesterol diet (days 10, 20, and 30). Linear regression analysis showed a positive correlation between these activities with correlation coefficients r = 0.959 for protein kinase C and phosphatidylcholine:ceramide-phosphocholine transferase, and r = 0.998 for protein kinase C and phosphatidylethanolamine:ceramide-phosphoethanolamine transferase. On the other hand, protein kinase C activation does not correspond to sphingomyelinase activity changes. These data suggest that protein kinase C activation observed in cholesterol-enriched plasma membranes is due to increased production of diacylglycerol and increased acylation of sphingosine to ceramide. |
| Splinter hemorrhages as a possible clinical manifestation of cholesterol crystal embolization Turakhia, A. K. and M. A. Khan (1990), J Rheumatol 17(8): 1083-6. Abstract: We describe a patient with cholesterol crystal embolization who demonstrated splinter hemorrhages of multiple fingernails and toenails as part of her clinical presentations. Our patient's clinical presentation, and review of the medical literature, raise the possibility that cholesterol crystal embolization may be associated with splinter hemorrhages. |
| Spontaneous cholesterol emboli presenting as livedo reticularis Brown, N. J. and H. J. Morgan (1992), J Tenn Med Assoc 85(2): 64. |
| Spontaneous cholesterol embolisation: a rare cause of bowel infarction Smith, F. C., A. Boon, et al. (1991), Eur J Vasc Surg 5(5): 581-2. |
| Spontaneous gallstone formation in deer mice: interaction of cholesterol, bile acids, and dietary fiber Ginnett, D. A., J. H. Theis, et al. (2003), J Wildl Dis 39(1): 105-13. Abstract: A study of the physiologic and ecologic factors involved in a spontaneous seasonal gallstone cycle of deer mice (Peromyscus maniculatus gambelii) was conducted at the Tulelake National Wildlife Refuge (California, USA) from March 1991 to June 1992. The specific hypothesis examined was whether or not seasonal increases in dietary fiber intake provides the necessary conditions for a solubility defect, or supersaturation mechanism, resulting in precipitation of cholesterol gallstones. Results indicated that in addition to the seasonal gallstone prevalence cycle, these deer mice exhibit significant seasonal cycling in serum cholesterol, serum bile acids, fecal bile acids, and diet composition. These physiologic and dietary cycles were phase-advanced 3 mo over the gallstone prevalence cycle, indicating an approximate 3 mo time period for gallstone formation under field conditions. Further, seasonal dietary fiber (plant material and seeds) was positively correlated with both serum cholesterol and the fecal bile acids. This suggests that in wild deer mice, variations in dietary fiber may significantly affect the resorption of bile acids, thereby providing a potential physiologic and nutritional mechanism for spontaneous cholesterol gallstone formation. |
| Spontaneous intermembrane transfer of various cholesterol-derived hydroperoxide species: kinetic studies with model membranes and cells Vila, A., W. Korytowski, et al. (2001), Biochemistry 40(48): 14715-26. Abstract: Whereas spontaneous and protein-mediated transfer/exchange of cholesterol (Ch) between membranes has been widely studied, relatively little is known about the translocation of Ch oxidation products, particularly hydroperoxide species (ChOOHs), which can act as cytotoxic prooxidants. A major aim of the present study was to examine and compare the intermembrane transfer characteristics of several biologically relevant ChOOH isomers, including singlet oxygen-derived 5alpha-OOH, 6alpha-OOH, and 6beta-OOH and free radical-derived 7alpha-OOH and 7beta-OOH. These species were generated in (14)CCh-labeled donor membranes erythrocyte ghosts or unilamellar DMPC/Ch (1.0:0.8 mol/mol) liposomes by means of dye-sensitized photoperoxidation. Spontaneous transfer to nonoxidized acceptor membranes (DMPC liposomes or ghosts, respectively) at 37 degrees C was monitored by thin-layer chromatography with phosphorimaging radiodetection (HPTLC-PI) or liquid chromatography with mercury cathode electrochemical detection HPLC-EC(Hg). The former allowed measurement of total (unresolved) ChOOH along with parent Ch, whereas the latter allowed measurement of individual ChOOHs. Ghost membranes in which approximately 4% of the Ch had been peroxidized, giving mainly 5alpha-OOH, transferred total ChOOH and Ch to liposomes in apparent first-order fashion, the rate constant for ChOOH being approximately 65 times greater. Like Ch desorption, ChOOH desorption from donor membranes was found to be rate limiting, and rate varied inversely with size when liposomal donors were used. For individual ChOOHs, rate constant magnitude (7alpha/7beta-OOH > 5alpha-OOH > 6alpha-OOH > 6beta-OOH) correlated inversely with reverse-phase HPLC retention time, suggesting that faster transfer reflects greater hydrophilicity. Liposome-borne ChOOHs exhibited the same order of toxicity toward COH-BR1 cells, which are deficient in ability to detoxify these peroxides. The prospect of disseminating oxidative cell injury via translocation of ChOOHs and other lipid hydroperoxides is readily apparent from these findings. |
| Spontaneous transfer of phospholipid and cholesterol hydroperoxides between cell membranes and low-density lipoprotein: assessment of reaction kinetics and prooxidant effects Vila, A., W. Korytowski, et al. (2002), Biochemistry 41(46): 13705-16. Abstract: Under oxidative pressure in the vascular circulation, erythrocytes and phagocytic cells may accumulate membrane lipid hydroperoxides (LOOHs), including cholesterol- and phospholipid-derived species (ChOOHs, PLOOHs). LOOH translocation from cells to low-density lipoprotein (LDL) might sensitize the latter to free radical-mediated oxidative modification, an early event associated with atherogenesis. To test this, we examined the spontaneous transfer kinetics of various ChOOH species (5 alpha-OOH, 6 alpha-OOH, 6 beta-OOH, 7 alpha/7 beta-OOH) and various PLOOH groups (PCOOH, PEOOH, PSOOH, SMOOH) using photoperoxidized erythrocyte ghosts as model donors and freshly prepared LDL as an acceptor. LOOH departure or uptake was monitored by reverse-phase HPLC with reductive electrochemical detection. Mildly peroxidized ghost membranes transferred overall ChOOH and PLOOH to LDL with apparent first-order rate constants approximately 60 and approximately 35 times greater than those of the respective parent lipids. Individual ChOOH rate constants decreased in the following order: 7 alpha/7 beta-OOH > 5 alpha-OOH > 6 alpha-OOH > 6 beta-OOH. Kinetics for reverse transfer from LDL to ghosts followed the same trend, but rates were significantly higher for all species and their combined activation energy was lower (41 vs 85 kJ/mol). PLOOH transfer rate constants ranged from 4- to 15-fold lower than the composite ChOOH constant, their order being as follows: PCOOH approximately PEOOH approximately PSOOH > SMOOH. Similar PLOOH transfer kinetics were observed when LDL acceptor was replaced by unilamellar liposomes, consistent with desorption from the donor membrane being the rate-limiting step. The susceptibility of transfer LOOH-enriched LDL to Cu2+-induced chain peroxidative damage was assessed by monitoring the accumulation of conjugated dienes and products of free radical-mediated cholesterol oxidation. In both cases, transfer-acquired LOOHs significantly reduced the lag time for chain initiation relative to that observed using nonperoxidized ghosts. These findings are consistent with the idea that LDL can acquire significant amounts of "seeding" LOOHs via translocation from various donors in the circulation. |
| Spontaneously low LDL cholesterol and reaction to exercise-induced stress Berg, A., M. Halle, et al. (1996), Lancet 347(8998): 405. |