Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apparent pressures in the surface monolayer of emulsion particles can be estimated by comparing the absorption of an apolipoprotein to planar lipid monolayers and to emulsions. Lipids are spread at an air-water interface in a Pockels/Langmuir surface balance and the adsorption of [14C]-labeled apolipoproteins placed in the subphase is studied as a function of surface pressure using the surface radioactivity method. An apoprotein surface concentration/initial lipid surface pressure curve (gamma/pi i) is constructed. The maximum apolipoprotein surface concentration gamma e of emulsions is derived from standard emulsion/apolipoprotein binding isotherms. The apparent emulsion surface pressure is then estimated by comparing gamma e to the gamma/pi i curve. Apolipoprotein A-I has been used as an example of a probe to estimate the effective surface pressure in approximately 1000 A diameter egg yolk phosphatidylcholine/cholesterol/triolein emulsion particles. When the cholesterol content of emulsions is low, the surface pressure of the emulsion is about 17 dyne cm-1. At high cholesterol concentrations (0.49 cholesterol/phospholipid mole ratio) the surface pressure is increased to 25 dyne cm-1. The addition of the maximum amounts of apoA-I to these particles raises the effective surface pressure of the emulsion to about 30 dyne cm-1 and stabilizes the particles.
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PMID:A technique to estimate the apparent surface pressure of emulsion particles using apolipoproteins as probes. 141 72

Confluent monolayers of the human hepatoblastoma-derived cell line, Hep G2, were incubated in serum-free medium. Conditioned medium was ultracentrifugally separated into d less than 1.063 g/ml and d 1.063-1.20 g/ml fractions since very little VLDL was observed. The d less than 1.063 g/ml fraction was examined by electron microscopy; it contained particles of 24.5 +/- 2.3 nm diameter, similar in size to plasma LDL; a similar size was demonstrated by nondenaturing gradient gel electrophoresis. These particles possessed apoB-100 only. The d less than 1.063 g/ml fraction had a lipid composition unlike that of plasma LDL; unesterified cholesterol was elevated, there was relatively little cholesteryl ester, and triglyceride was the major core lipid. The d 1.063-1.20 g/ml fraction was heterogeneous in size and morphology. Electron microscopy revealed discoidal particles (14.9 +/- 3.2 nm long axis and 4.5 +/- 0.2 nm short axis) as well as small spherical ones (7.6 +/- 1.4 nm diameter). Nondenaturing gradient gel electrophoresis consistently showed the presence of peaks at 13.4 11.9, 9.7, and 7.4 nm. The latter peak was conspicuous and probably corresponded to the small spherical structures seen by electron microscopy. Unlike plasma HDL, Hep G2 d 1.063-1.20 g/ml lipoproteins contained little or no stainable material in the (HDL3a)gge region by gradient gel electrophoresis. Hep G2 d 1.063-1.20 g/ml lipoproteins differed significantly in composition from their plasma counterparts; unesterified cholesterol and phospholipid were elevated and the mole ratio of unesterified cholesterol to phospholipid was 0.8. Cholesteryl ester content was extremely low. ApoA-I was the major apolipoprotein, while apoE was the next most abundant protein; small quantities of apoA-II and apoCs were also present. Immunoblot analysis of the d 1.063-1.20 g/ml fraction after gradient gel electrophoresis showed that apoE was localized in the larger pore region of the gel (apparent diameter greater than 12.2 nm); the apoA-I distribution in this fraction was very broad (7.1-12.2 nm), and included a distinct band at 7.4 nm. Immunoblotting after gradient gel electrophoresis of concentrated medium revealed that a significant fraction of apoA-I in the uncentrifuged medium was in a lipid-poor or lipid-free form. This cell line may be a useful model for investigating the metabolism of newly formed HDL.
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PMID:Characterization of lipoproteins produced by the human liver cell line, Hep G2, under defined conditions. 301 29

Human carriers of apolipoprotein A-I(Milano) (Arg173 --> Cys substitution in apolipoprotein A-I) are characterized by an HDL deficiency in which small, dense HDL accumulate in plasma. Because affected individuals are heterozygous for this mutation, the full impact of apolipoprotein A-I(Milano) (apoA-I(Milano)) on HDL-cholesterol metabolism is unknown. In this study, apoA-I(Milano) transgenic mice were used to evaluate the extent of apoA-I(Milano) dimerization and HDL particle size restriction in the absence of wild-type apoA-I. Murine apoA-I knockout mice were utilized to express apoA-I(Milano) and human apoA-II in the presence of wild-type, human apoA-I (apoA-IMilano/A-Iwt/A-II) and in its absence (apoA-IMilano/A-II). Plasma HDL-cholesterol concentrations were similar (30 mg/dl) in both lines of apoA-I(Milano) transgenic mice. In the apoA-IMilano/A-Iwt/A-II phenotype, 14% of the apoA-I(Milano) formed homodimers and 33% formed heterodimers with apoA-II. ApoA-I(Milano) homodimers increased by 71% in the apoA-IMilano/A-II transgenics and was associated with an abundance of small, 7.6-nm HDL3-sized particles compared to the 9.5, 8.3, and 7.6-nm-sized particles in apoA-IMilano/A-Iwt/A-II mice. The unesterified cholesterol/cholesteryl ester mole ratio of HDL was elevated by 45% in apoA-IMilano/A-Iwt/A-II mice and by 90% in apoA-IMilano/A-II transgenics compared to wild-type (human apoA-I/A-II). Both apoA-I(Milano) transgenics possessed normal levels of plasma LCAT activity, but endogenous cholesterol esterification rates were reduced by 50% compared to controls. Thus, HDL particle size restriction was not the result of impaired LCAT activation; rather, dimerization of apoA-I(Milano) limited the esterification of cholesterol on endogenous HDL. In the absence of wild-type apoA-I, the more extensive dimerization of apoA-I(Milano) severely limited cholesteryl ester accumulation on plasma HDL accounting for the abundance of small, 7.6-nm HDL3 particles in apoA-IMilano/A-II mice.
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PMID:High density lipoprotein particle size restriction in apolipoprotein A-I(Milano) transgenic mice. 939 29

Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endogenously produced apoE in mediating the recruitment of cellular cholesterol. THP-1 human monocytes were differentiated (300 nm phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 microg protein/ml). ApoA-I (10 microg/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied by a significant increase in the UC/PL mole ratio of nascent HDL (UC/PL = 0.80 +/- 0.15) in the medium compared to complexes isolated from macrophages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were formed in incubations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absence of apoA-I. Despite the increase in medium apoE accumulation, a majority (85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macrophage-foam cells possessed apoA-I without apoE. ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL represents a major metabolic pathway of cellular cholesterol recruitment compared to the endogenous production of apoE.
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PMID:Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells. 986 53