Functional Roles of Plasma High Density Lipoprotein

Scanu, Angelo M.; Byrne, Robert; Mihovilovic, Mirta

doi:10.3109/10409238209108711

Cited by 44 publications

(12 citation statements)

References 162 publications

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“…ApoA-1 on HDL mediates reverse cholesterol transport and metabolism and provides a cofactor for the enzyme 1ecithin:cholesterol acyltransferase (Fielding and Fielding, 1981). ApoA-2 has been inferred to importantly influence the HDL structural states, enhance HDL stability, and regulate the kinetics of apoA-1 transfer (reviewed by Scanu et al, 1982;Hedrick and Lusis, 1994). In contrast to apoA-1, which readily transfers among HDL particles in the course of their metabolism, apoA-2 is more strongly associated with HDL and has Reprint requests to: Olga Gursky, Department of Biophysics, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts 02 11 8; e-mail: gursky@rned-biophd.bu.edu.…”

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confidence: 99%

High‐ and low‐temperature unfolding of human high‐density apolipoprotein A‐2

Gursky

Atkinson

1996

Protein Science

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Human plasma apolipoprotein A-2 (apoA-2) is the second major protein of the high-density lipoproteins that mediate the transport and metabolism of cholesterol. Using CD spectroscopy and differential scanning calorimetry, we demonstrate that the structure of lipid-free apoA-2 in neutral low-salt solutions is most stable at -25 "C and unfolds reversibly both upon heating and cooling from 25 "C. High-temperature unfolding of apoA-2, monitored by far-UV CD, extends from 25-85 "C with midpoint Th = 56 2 2 "C and vant Hoff's enthalpy AH(Th) = 17 2 2 kcal/mol that is substantially lower than the expected enthalpy of melting of the a-helical structure. This suggests low-cooperativity apoA-2 unfolding. The apparent free energy of apoA-2 stabilization inferred from the CD analysis of the thermal unfolding, AG,,,,(25") = 0.82 ? 0.15 kcal/mol, agrees with the value determined from chemical denaturation. Enhanced lowtemperature stability of apoA-2 observed upon increase in Na,HPO, concentration from 0.3 mM to 50 mM or addition of 10% glycerol may be linked to reduced water activity. The close proximity of the heat and cold unfolding transitions, that is consistent with low AG,pp(250), indicates that lipid-free apoA-2 has a substantial hydrophobic core but is only marginally stable under near-physiological solvent conditions. This suggests that in vivo apoA-2 transfer is unlikely to proceed via the lipid-free state. Low AH(T,) and low apparent ACp -0.52 kcal/mol.K inferred from the far-UV CD analysis of apoA-2 unfolding, and absence of tertiary packing interactions involving Tyr groups suggested by near-UV CD, are consistent with a molten globular-like state of lipid-free apoA-2.

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confidence: 99%

High‐ and low‐temperature unfolding of human high‐density apolipoprotein A‐2

Gursky

Atkinson

1996

Protein Science

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“…Several factors may have contributed to these events. Possibly once the HDL particles became coated by Triton, they could no longer interact physiologically with other plasma lipoprotein systems, enzymes, or membrane receptors 16 and so they underwent cellular uptake by nonspecific mechanisms. The involvement of the reticulo-endothelial system in dogs receiving Triton WR-1339 has been documented.…”

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confidence: 99%

In vitro and in vivo interactions of Triton 1339 with plasma lipoproteins of normolipidemic rhesus monkeys. Preferential effects on high density lipoproteins.

Yamamoto¹,

Shen²,

Zarins³

et al. 1984

Arteriosclerosis

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Triton WR-1339 was incubated in vitro in various proportions with plasma from normolipidemic rhesus monkeys or with ultracentrifugally purified lipoproteins, and the products were examined by isopycnic density gradient ultracentrifugation, agarose column chromatography, electrophoretic and immunochemical techniques, and electron microscopy. Some experiments used apo A-l, apo A-ll, or Triton labeled with either 125 I or 1 3 1 I. At concentrations of less than 10 mg/ml plasma, Triton interacted preferentially with HDL, changing lipoprotein size and density; Triton was progressively incorporated into the HDL particles, displacing apo E, apo A-l, and apo A-ll. At concentrations above 10 mg/ml plasma, Triton displaced all apo A-l from the particle, and much lipid was dissolved into the Triton micelles. When Triton-treated HDL particles were used as a substrate for the enzyme LCAT, enzyme activity decreased in parallel to the displacement of apo A-l. There was no displacement of apo B from LDL nor any loss of lipids; but the particles became deformed and formed rouleaux.A single intravenous dose of Triton WR-1339 administered to a normolipidemic monkey (N) and to a hypercholesterolemic monkey (H) resulted in concentrationdependent HDL changes similar to those observed in vitro. LDL was less affected by Triton, with changes occurring only at high doses. After these structural changes, intravenously injected 131 I apo A-l disappeared rapidly from the circulation; 125 I apo A-II disappeared less rapidly. These increased clearances were accompanied by a drop in apo A-l plasma levels and the disappearance of HDL particles from plasma. The lipoprotein and apolipoprotein patterns returned to normal 14 days after Triton.We conclude that Triton WR-1339, when exposed to rhesus plasma in vitro or in vivo, interacts preferentially with HDL in a dose-dependent manner. At low concentrations, Triton acts on surface components of the HDL particle; at higher concentrations, Triton penetrates the particle, causing structural disruption. Because of its high affinity for HDL, Triton WR-1339 is a useful reagent for study of HDL structure-function relationships.

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“…It has been demonstrated that some mitogenic peptides (i.e., platelet-derived growth factor) are potent activators of endogenous phospholipase C activity in 3T3 cell plasma membranes (Habenicht et al, 1981). Since HDL apolipoproteins are known to activate (or inhibit) lipoprotein lipase (Scanu et al, 1982), it is tempting to speculate that one or more of these apolipoproteins may also activate (or inhibit) endogenous lipase, such as phospholipase C. If so, apolipoproteins (specifically apoA-I and apoC-110 may modulate mitogenesis in WTlA cells by acting through the same pathways as other mitogenic growth factors. Our attempts at mimicking the growth promoting effects of apoHDL on WTlA cell by use of exogenous phospholipase C from C. perfringens have met with little success.…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, the functional roles of this lipoprotein class in serum-free medium have been obscure. This has been due mostly to the structural complexity of the HDL molecule, which consists of a neutral lipid core (mainly cholesterol ester) surrounded by a complex of several different apolipoproteins and phospholipids (largely phosphatidylcholine) held together by non-covalent bonds (Scanu et al, 1982).For many of the cells exhibiting a growth requirement for HDL under serum-free conditions, the HDL supplement can be replaced with cholesterol (Kawamoto et al, 1983), unsaturated fatty acids (Chen et al, 1984), biotin and choline (Cohen and Gospodarowicz, 1985), and/or liposomes made of egg yolk phosphatidylcholine (Fujii et al, 19831, indicating that one of the functions of HDL is to provide cells with preformed lipids. In these instances, the apolipoprotein constituents of HDL, which are responsible for solubilizing the lipids associated with HDL, probably regulate the interaction (or uptake) of HDL-associated lipid with the cell.…”

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confidence: 99%

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confidence: 99%

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Purified HDL‐apolipoproteins, A‐I and C‐III, substitute for HDL in promoting the growth of SV40‐transformed REF52 cells in serum‐free medium

Chen

Labrake‐Farmer

McClure

1986

Journal Cellular Physiology

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The lipid-free apolipoproteins of human high density lipoprotein (HDL) have been assayed for their ability to substitute for native HDL in promoting the growth of a SV40-transformed REF52 cell line in serum-free medium. Total HDL-apolipoproteins (apoHDL) were found to mimic almost exactly the growth promoting effects of whole HDL. The apoHDL-associated growth promoting activity eluted from a Sephacryl S-200 column in two separate fractions coinciding with the protein peaks of apolipoprotein A-I and the C group of apolipoproteins. These two fractions, designated S-II and S-IV, respectively, acted additively in promoting WT1A cell growth when tested at saturating concentrations. The active component in the S-II fraction maximally stimulated WT1A cell growth at 40-60 micrograms/ml and was identified as apolipoprotein A-1 by NaDodSO4 polyacrylamide gel electrophoresis and affinity chromatography on anti-(apoA-I). The active component in the S-IV fraction was maximally active at 1-2 micrograms/ml and was identified as apolipoprotein C-III by DEAE ion exchange high pressure liquid chromatography and polyacrylamide gel electrophoresis (at pH 8.3) in 6 M urea. These results indicate that the growth promoting effect of HDL on WT1A cells is mediated via the HDL-apolipoproteins, A-I and C-III, and that the mechanism responsible does not necessarily involve their participation in the uptake (or utilization) of HDL-associated lipids.

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Functional Roles of Plasma High Density Lipoprotein

Cited by 44 publications

References 162 publications

High‐ and low‐temperature unfolding of human high‐density apolipoprotein A‐2

High‐ and low‐temperature unfolding of human high‐density apolipoprotein A‐2

In vitro and in vivo interactions of Triton 1339 with plasma lipoproteins of normolipidemic rhesus monkeys. Preferential effects on high density lipoproteins.

Purified HDL‐apolipoproteins, A‐I and C‐III, substitute for HDL in promoting the growth of SV40‐transformed REF52 cells in serum‐free medium

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