diphenylhexatriene and cholesteryl-oleate

Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.

Topics: Apolipoproteins E; Carcinoma, Hepatocellular; Cell Line; Cholesterol Esters; Diphenylhexatriene; Emulsions; Fluorescence Polarization; Humans; Liver; Liver Neoplasms; Particle Size; Structure-Activity Relationship; Triglycerides; Triolein

Low density lipoproteins (LDL) consist of an apolar core of cholesterol esters and triglycerides surrounded by a monolayer of phospholipid, cholesterol, and a single molecule of apolipoprotein B (apoB-100). To determine the influence of core and surface constituents on the surface of LDL, we have measured core and surface order parameters for native LDL, and reconstituted LDLs (rLDL) whose apolar core lipids were extracted and replaced with either cholesterol oleate (CO) or triolein (TO). Order parameters were measured by fluorescence depolarization of diphenylhexatriene (DPH), which is located primarily in the core, and of trimethylammoniumdiphenylhexatriene (TMA-DPH), which is anchored at the water-phospholipid interface. DPH order parameters for LDL reconstituted with TO (r-[TO]LDL) were much lower than those for LDL reconstituted with CO (r-[CO]LDL), consistent with the physical properties of TO, a nonviscous liquid at all temperatures studied, and CO, which exists in a liquid crystalline or viscous liquid state at the temperatures studied. Although core cholesterol esters in r[CO]LDL and native LDL undergo distinct order-disorder transitions, these transitions were not detected by DPH. This is most likely due to the difference between the time scale for end-over-end tumbling of cholesterol esters and the fluorescence lifetime of DPH. Despite the fact that the core lipids of r-[CO]LDL were much more ordered than those of r-[TO]LDL, surface order parameters for both lipoproteins were similar. We conclude that the motional states of the core and surface lipids are relatively independent. Surface order parameters for native LDL were higher than those for reconstituted LDLs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cholesterol Esters; Diphenylhexatriene; Fluorescence Polarization; Humans; Lipids; Lipoproteins, LDL; Triolein