Interaction of plasma apolipoproteins with lipid monolayers

doi:10.1016/0005-2736(79)90126-3

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 556, Issue 3, 5 October 1979, Pages 369-387

https://doi.org/10.1016/0005-2736(79)90126-3 Get rights and content

Abstract

The monolayer technique has been used to study the interaction of lipids with plasma apolipoproteins. Apolipoprotein C-II and C-III from human very low density lipoproteins, apolipoprotein A-I from human high density lipoproteins and arginine-rich protein from swine very low density lipoproteins were studied. The injection of each apoprotein underneath a monolayer of egg phosphatidyl[¹⁴C]choline at 20 mN/m caused an increase in surface pressure to approximately 30 mN/m. With apolipoprotein C-II and apolipoprotein C-III there was a decrease in surface radioactivity indicating that the apoproteins were removing phospholipid from the interface; the removal of phospholipid was specific for apolipoprotein C-II and apolipoprotein C-III. Although there was a removal of phospholipid from the monolayer, the surface pressure remained constant and was due to the accumulation of apoprotein at the interface. The rate of surface radioactivity decrease was a function of protein concentration, required lipid in a fluid state and, of the lipids tested, was specific for phosphatidylcholine. Cholesterol and phosphatidylinositol were not removed from the interface. The addition of 33 mol% cholesterol to the phosphatidylcholine monolayer did not affect the removal of phospholipid by apolipoprotein C-III.

The addition of phospholipid liposomes to the subphase greatly facilitated the apolipoprotein C-II-mediated removal of phospholipid from the interface.

References (36)

P. Alaupovic
Atherosclerosis
(1971)
A.M. Scanu et al.
J.C. Osborne et al.
Adv. Protein Chem.
(1977)
J.D. Morrisett et al.
Biochim. Biophys. Acta
(1977)
E.J. Schaefer et al.
J. Lipid Res.
(1978)
A.L. Catapano et al.
J. Lipid Res.
(1978)
R.L. Jackson et al.
J. Lipid Res.
(1977)
G.R. Bartlett
J. Biol. Chem.
(1959)
L.L.M. Van Deenen et al.
Adv. Lipid Res.
(1964)
R.A. Demel et al.
Biochim. Biophys. Acta
(1977)

G.R. Schacterle et al.

Anal. Biochem.

(1973)

M.C. Glangeaud et al.

Biochim. Biophys. Acta

(1977)

R.O. Scow et al.

Biochim. Biophys. Acta

(1976)

C. Ehnholm et al.

J. Biol. Chem.

(1975)

S. Eisenberg

Biochim. Biophys. Acta

(1977)

R.A. Demel et al.

Biochim. Biophys. Acta

(1975)

D.R. Illingworth et al.

Biochim. Biophys. Acta

(1972)

S. Eisenberg

J. Lipid Res.

(1978)

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We hypothesized that apoC-II removes POPC molecules from POPC/TO/W interfaces as protein molecules desorb from the interface. A previous study at the PC/air/water interface showed that apoC-II, when injected into the subphase, decreased the surface radioactivity of monolayers of egg phosphatidyl[14C]choline (47). Consistent with these data, apoC-II removed POPC from POPC/TO/W interfaces (Fig. 9).
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Apolipoproteins C-I and C-III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets
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Citation Excerpt :
The presence of smaller sized particles can probably explain why as much as 60% of the enzyme passed through the filter when rat lymph chylomicrons were used because the chylomicrons were not washed by floatation. Others have reported that apoC-III is able to remove phospholipids from monolayers (50). We found that the majority of the added apoC-III did not pass the syringe filters.
Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4.
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Molecular mechanisms of the red cell storage lesion
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Preserved erythrocytes undergo several changes during storage, collectively referred to as the storage lesion, which reduce the effectiveness of stored erythrocytes following transfusion. This review describes the mechanisms leading to these changes, so far as they are known, and discusses the relationship of the changes to one another and how they contribute to the diminished function of stored erythrocytes.
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1986, Advances in Protein Chemistry
All cells make proteins that are destined for non-cytoplasmic locations, such as the extracellular fluid, the lumina of organelles, or the cell membranes. These proteins are almost invariably synthesized in the cytoplasm. Thus, such a protein must cross or enter one or more membranes in order to reach its destination. Furthermore, this process is specific in a manner that a particular protein travels only to its proper location, and only proteins destined for a particular location are transported there. The molecular mechanism of these processes has been the subject of intense investigation in the last decade. Most knowledge concerning the secretory process has come from genetic and biochemical studies. More recently, however, biophysical techniques have been used to investigate properties of the secretory apparatus and the signal sequence. The aim of this chapter is to describe the requirement for protein secretion and also to evaluate hypotheses of the ways in which secretion occurs. Particular emphasis is given to the role of the signal sequence.
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The effect of lipid composition and structure on the lipoprotein lipase-catalyzed hydrolysis of triacylglycerols was determined in a monolayer system consisting of purified bovine milk lipoprotein lipase and fatty acid-free albumin. In a monolayer of dioleoylphosphatidylcholine containing 1–6 mol% of either tri[¹⁴C]oleoylglycerol or tri[¹⁴C]palmitoylglycerol, lipoprotein lipase catalyzed the hydrolysis of the unsaturated triacylglycerol at a higher rate than the saturated lipid and in either the presence or absence of apolipoprotein C-II, the activator protein for the enzyme. For example, with 3 mol% triacylglycerol and in the presence of apolipoprotein C-II, the rate of the lipoprotein lipase-catalyzed hydrolysis of tri[¹⁴C]oleoylglycerol was 27 μmol oleic acid produced/h per mg enzyme vs. 12 μmol for tri[¹⁴C]palmitoylglycerol. The effect of phospholipid fatty acyl chain length and unsaturation/saturation, polar head group and surface density on the lipoprotein lipase-catalyzed hydrolysis of tri[¹⁴C]oleoylglycerol was determined. The rate of enzyme hydrolysis of triacylglycerol was similar whether the phospholipid was a diester or diether lipid or the polar head group was ethanolamine or choline. In general, phospholipids with shorter and unsaturated fatty acyl chains gave higher rates of lipoprotein lipase hydrolysis of triacylglycerol than the corresponding longer and saturated lipids. However, with all phospholipids tested, the rate of enzyme hydrolysis decreased with increasing surface density. Lipoprotein lipase showed no activity toward triacylglycerol in a monolayer of sphingomyelin; addition of dioleoylphosphatidylcholine to the monolayer enhanced the rate of enzyme catalysis. Cholesterol (50 mol%) in a dipalmitoylphosphatidylcholine monolayer increased the rate of the lipoprotein lipase-catalyzed hydrolysis of tri[¹⁴C]oleoylglycerol, whereas cholesterol decreased the rate in a dioleoylphosphatidylcholine monolayer. The effect of phospholipid structure and surface density on lipoprotein lipase activity could not be accounted for by the amount of apolipoprotein C-II which was present at the interface. Based on these findings and other reports in the literature, we suggest that the catalytic activity of lipoprotein lipase toward tri[¹⁴C]oleylglycerol in various monolayers is dependent on the conformation or appropriate physical state of the triacylglycerol substrate at the lipid interface.

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^∗: Present address: Universität Bern, Freiestrasse 1, Bern, Switzerland.

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Interaction of plasma apolipoproteins with lipid monolayers

Abstract

Atherosclerosis

Adv. Protein Chem.

Biochim. Biophys. Acta

J. Lipid Res.

J. Lipid Res.

J. Lipid Res.

J. Biol. Chem.

Adv. Lipid Res.

Biochim. Biophys. Acta

Anal. Biochem.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Biol. Chem.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Lipid Res.