The interaction of prostaglandins with human serum lipoproteins

Using high density and low density lipoproteins (HDL and LDL) labeled with fluorescent analogues of phosphatidylcholine or sphingomyelin it was found that low amounts (10^–12 M) of prostaglandins E₁ and F₂ induced different structural rearrangements of the lipoprotein surface, whereas prostaglandins E₂ and F₁ had no effect. The effects of prostaglandin E₁ on HDL were largely paralled by those of this prostaglandin on synthetic recombinants prepared from pure apolipoprotein A₁, phospholipids and cholesterol and were demonstrated to be caused by prostaglandin-apolipoprotein interaction. The interaction resembled that of a ligand with a specific receptor protein because it was specific, reversible, concentration and temperature dependent and saturable. However the retaining capacity of HDL or LDL for prostaglandin E₁ as determined by equilibrium dialysis was very low and a single prostaglandin E₁ molecule was able to induce structural changes in large numbers of discrete lipoprotein particles. To explain this remarkable fact a non-equilibrium model of ligand-receptor interaction is proposed. According to that model in open systems characterized by weak ligand-receptor binding, high diffusion rate of the ligand and long relaxation times which exceed the interval between two successive receptor occupations, the ligand-induced changes will accumulate, resulting in transformation of the system into a new state which may be far away from equilibrium. It is emphasized that the low mobility of lipids constituting the environment of the receptor protein plays a critcal role in this type of signal amplification.It was further demonstrated that the PGE₁-induced changes of the lipoprotein surface resulted in an enhancement of LDL-to-HDL transfer of cholesterol esters and phosphatidylcholine especially in the presence of serum lipid transfer proteins. The acceleration of the interlipoprotein transfer caused by prostaglandin E₁ in turn increases the rate of cholesterol esterification in serum. It is suggested that in such a way prostaglandin E₁ may influence the homeostasis of cholesterol.Abbreviations LDL low density lioproteins - HDL high density lipoproteins - PG prostaglandin - ASM anthrylvinyl-labeled sphingomyelin (N-12-(9-anthryl)-11-trans-dodecanoylsphingosin-1-phosphocholine - APC anthrylvinylphosphatidylcholine (1-radyl-2-(9-anthryl)-11-transdodecanoyl)-sn-glycerophosphocholine - NAP-SM nitroazidophenyl labeled sphingomyelin (N-N-(2-nitro-4azidophenyl)-12-aminododecanoyl]-sphingosin-1-phosphocholine) - NAP-PC adizophenyl labeled phosphatidylcholine (1-radyl-2-N-(2-nitro-4azidophenyl)-12-aminododecanoyl]-sn-glycero-3-phosphocholine - DPPC dipalmitoylphosphatidylcholine - P fluorescence polarization - E parameter of tryptophanyl to ASM resonance energy transfer - LEP lipid-exchange protein