Kinetics of lipid-protein interactions: effect of cholesterol on the association of human plasma high-density apolipoprotein A-I with L-.alpha.-dimyristoylphosphatidylcholine

Pownall, Henry J.; Massey, John B.; Kusserow, Steven K.; Gotto, Antonio M.

doi:10.1021/bi00571a004

Cited by 111 publications

(77 citation statements)

References 26 publications

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“…Similar to other studies, the rates of solubilization were highly dependent upon temperature and sterol concentration [28][29][30]. Cholesterol, lathosterol and β-sitosterol, all which form ordered lipid phases, enhance the rate of solubilization.…”

Section: Introductionsupporting

confidence: 84%

“…The two apoA-I molecules wrap around a lipid bilayer disk forming two stacked rings (double belt) in an antiparallel orientation. However, larger sized rHDL containing 3 and 4 molecules of apoA-I can be formed in the presence of cholesterol both by DMPC solubilization [28][29][30] and by cholate dialysis methods [31,32]. Incubating apoA-I with cells expressing ABCA1 also generates numerous discrete particles that vary in size (diameters from ~ 90-200 Å) and number of apoA-I molecules (from 2 to 8 molecules) [25,26,33,34].…”

Section: Introductionmentioning

confidence: 99%

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Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Massey

Pownall

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Formation of discoidal high density lipoproteins (rHDL) by apolipoprotein A-I (apoA-I) mediated solubilization of dimyristoyl phosphatidylcholine (DMPC) multilamellar vesicles (MLV) was dramatically affected by bilayer cholesterol concentration. At a low ratio of DMPC/apoA-I (2 mg DMPC/mg apoA-I, 84/1 mol/mol), sterols (cholesterol, lathosterol, and β-sitosterol) that form ordered lipid phases increase the rate of solubilization similarly, yielding rHDL with similar structures. By changing the temperature and sterol concentration, the rates of solubilization varied almost 3 orders of magnitude; however, the sizes of the rHDL were independent of the rate of their formation and dependent upon the bilayer sterol concentration. At a high ratio of DMPC/apoA-I (10/1 mg DMPC/mg apoA-I, 420/1 mol/mol), changing the temperature and cholesterol concentration yielded rHDL that varied greatly in size, phospholipid/protein ratio, mol% cholesterol, and number of apoA-I molecules per particle. rHDL were isolated that had 2, 4, 6, and 8 molecules of apoA-I per particle, mean diameters of 117, 200, 303, and 396 Å, and a mol% cholesterol that was similar to the original MLV. Kinetic studies demonstrated the different sized rHDL are formed independently and concurrently. The rate of formation, lipid composition, and three-dimensional structures of cholesterol-rich rHDL are dictated primarily by the original membrane phase properties and cholesterol content. The size speciation of rHDL and probably nascent HDL formed via the activity of the ABCA1 lipid transporter are mechanistically linked to the cholesterol content of the membranes from which they were formed.

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Section: Introductionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Massey

Pownall

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…However, if therapeutic applications of L-ADM are contemplated, PG should be preferred to PS because it is less sensitive to lipid oxidation processes affecting the head group (Roseman et al, 1975) and can be readily obtained from animal sources by a simpler enzymatic conversion of PC (Comfurius & Zwaal, 1977). The fact that the Chol: phospholipid molar ratio can be decreased to 25% without any significant loss of anti-tumour activity is consistent with the ability of liposomes to withstand the deleterious effect of serum proteins when the Chol content is kept above 20% (Pownall et al, 1979;Snyder & Freire, 1980). This reduction of Chol content is important as it allows to reduce the lipid load necessary to deliver therapeutic doses of ADM.…”

Section: Discussionmentioning

confidence: 86%

Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model

Gabizón¹,

Goren²,

Fuks³

et al. 1985

Br J Cancer

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The use of liposomes as carriers of adriamycin (ADM) seems to offer important advantages with regard to the attenuation of the dose-dependent anthracycline-induced cardiomyopathy. This effect has been shown in rodents (Rahman et al., 1980(Rahman et al., , 1982Forssen & Tokes, 1981;Olson et al., 1982) and dogs (Herman et al., 1983) and is apparently related at least partially to the reduced uptake of the drug in the cardiac tissue of animals treated with liposome-entrapped ADM (L-ADM) (Forssen & Tokes, 1979, 1983 Rahman et al., 1980;Gabizon et al., 1982Gabizon et al., , 1983Olson et al., 1982). Obviously, if this delivery system is to be useful therapeutically, it is crucial to evaluate its anti-tumour activity. Since liposomes home preferentially in tissues with sinusoidal capillaries and rich in cells of the reticuloendothelial system, such as the liver and spleen (Segal et al., 1974;Poste et al., 1982), it is reasonable to assume that tumour colonies residing in these organs constitute a suitable target for liposome-mediated delivery of cytotoxic drugs. The purpose of this paper is to describe the antitumour In previous studies we showed that liposomes containing negatively charged phospholipids capture ADM very efficiently and cause important changes in the tissue distribution of the drug, viz. decreased levels in the heart and increased and sustained levels in the liver and spleen. These changes were observed in normal (Gabizon et al., 1982) and in tumour-bearing mice (Gabizon et al., 1983). Furthermore, when metastatic tumour cells were isolated from the liver we found significantly higher intracellular levels of ADM in tumour cells of mice treated with L-ADM as compared to free ADM treatment. Also, the proliferative ability of intrahepatic metastatic cells in in vitro qultures and in vivo transfer assays was markedly more impaired after L-ADM treatment than after ADM alone (Gabizon et al., 1983).These results, and especially the ability of liposomes to increase the intracellular levels of ADM in liver-residing tumour cells, provided a rational basis for therapeutic experiments. In the present study, we have compared the survival of tumour-inoculated mice treated either with L-ADM or with free ADM using the metastatic liver model of the J-6456 lymphoma. Our results suggest that the therapeutic index of ADM can be significantly improved by liposome association in a group of

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“…It is well established that the defects stimulate ion permeability (37,38) and the rate of flip-flop of PLs (39). Similarly, the microsolubilization of multilamellar vesicles of dimyristoylphosphatidylcholine by apoA-I is accelerated at the T M (?24jC), at which the gel and L d phases coexist and lattice defects occur (40)(41)(42). It has been established that PLs undergo phase transition in clusters, consisting of ?100 PLs, and the size of these clusters is proportional to the cooperativity of the transition (43).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I

Fukuda

Nakano

Sriwongsitanont

et al. 2007

Journal of Lipid Research

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Nascent HDL is known to be formed by the interaction of apolipoprotein A-I (apoA-I) with transmembrane ABCA1, but the molecular mechanism by which nascent HDL forms is less well understood. Here, we studied how reconstituted high density lipoprotein (rHDL) forms spontaneously on the interaction of apoA-I with model membranes. The formation of rHDL from pure phosphatidylcholine (PC) large unilamellar vesicles (LUVs) proceeded very slowly at 37.0jC, but sphingomyelin (SM) -rich PC/SM LUVs, which are in a gel/liquid-disordered phase (L d phase) at this temperature, were rapidly microsolubilized to form rHDL by apoA-I. The addition of cholesterol decreased the rate at which rHDL formed and induced the selective extraction of lipids by apoA-I, which preferably extracted lipids of L d phase rather than lipids of liquid-ordered phase. In addition, apoA-I extracted lipids from the outer and inner leaflets of LUVs simultaneously. These results suggest that the heterogeneous interface of the mixed membranes facilitates the insertion of apoA-I and induces L d phase-selective but leaflet-nonselective lipid extraction to form rHDL; they are compatible with recent cell works on apoA-I-dependent HDL generation.-Fukuda, M., M. Nakano, S. Sriwongsitanont, M. Ueno, Y. Kuroda, and T. Handa. Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I. J. Lipid Res. 2007. 48: 882-889.

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Kinetics of lipid-protein interactions: effect of cholesterol on the association of human plasma high-density apolipoprotein A-I with L-.alpha.-dimyristoylphosphatidylcholine

Cited by 111 publications

References 26 publications

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model

Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I

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