Functional expression of human and mouse plasma phospholipid transfer protein: effect of recombinant and plasma PLTP on HDL subspecies

Albers, John J.; Wolfbauer, Gertrud; Cheung, Marian C.; Day, Joseph R.; Ching, Andrew; Lok, Si; Tu, An Yue

doi:10.1016/0005-2760(95)00091-p

Cited by 126 publications

(127 citation statements)

References 21 publications

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“…When these results are considered with the data in Table IV, it follows that enrichment with TG destabilizes the apoA-I in rHDL. DISCUSSION The ability of PLTP to remodel HDL into large and small particles, mediate the dissociation of apoA-I from HDL, and transfer phospholipids between HDL and other lipoproteins is well documented (1)(2)(3)(4)(5)(6)(7)(8). Earlier work from this laboratory has also established that TG enrichment enhances the remodeling of HDL by PLTP (9).…”

Section: H (Closed Triangles)mentioning

confidence: 85%

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The Mechanism of the Remodeling of High Density Lipoproteins by Phospholipid Transfer Protein

Settasatian¹,

Duong²,

Curtiss³

et al. 2001

Journal of Biological Chemistry

114

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Phospholipid transfer protein (PLTP) remodels high density lipoproteins (HDL) into large and small particles. It also mediates the dissociation of lipid-poor or lipid-free apolipoprotein A-I (apoA-I) from HDL. Remodeling is enhanced markedly in triglyceride (TG)-enriched HDL (Rye, K.-A., Jauhiainen, M., Barter, P. J., and Ehnholm. C. (1998) J. Lipid. Res. 39, 613-622). This study defines the mechanism of the remodeling of HDL by PLTP and determines why it is enhanced in TG-enriched HDL. Homogeneous populations of spherical reconstituted HDL (rHDL) containing apoA-I and either cholesteryl esters only (CE-rHDL; diameter 9.3 nm) or CE and TG in their core (TG-rHDL; diameter 9.5 nm) were used. After 24 h of incubation with PLTP, all of the TG-rHDL, but only a proportion of the CE-rHDL, were converted into large (11.3-nm diameter) and small (7.7-nm diameter) particles. Only small particles were formed during the first 6 h of incubation of CE-rHDL with PLTP. The large particles and dissociated apoA-I were apparent after 12 h. In the case of TG-rHDL, small particles appeared after 1 h of incubation, while dissociated apoA-I and large particles were apparent at 3 h. The composition of the large particles indicated that they were derived from a fusion product. Spectroscopic studies indicated that the apoA-I in TG-rHDL was less stable than the apoA-I in CE-rHDL. In conclusion, these results show that (i) PLTP mediates rHDL fusion, (ii) the fusion product rearranges by two independent processes into small and large particles, and (iii) the more rapid remodeling of TG-rHDL by PLTP may be due to the destabilization of apoA-I. Phospholipid transfer protein (PLTP)1 transfers phospholipids (PL) between high density lipoproteins (HDL) and very low density lipoproteins as well as between different particles within the HDL fraction (1, 2). It also remodels HDL into large and small particles in a process that is accompanied by the dissociation of lipid-poor or lipid-free apolipoprotein A-I (apoA-I) (3-8). Remodeling is enhanced markedly in HDL that contain triglyceride (TG) in their core (9). Evidence of the importance of PLTP in HDL metabolism comes from studies of mice transgenic for human PLTP. These animals have increased levels of pre-␤ 1 -migrating HDL, the initial acceptors of cellular cholesterol in the first step of the reverse cholesterol pathway, and are also resistant to intracellular cholesterol accumulation (10 -12). Studies of PLTP knockout mice have shown that PLTP is essential for maintaining normal HDL levels in plasma (13). Moreover, it has been reported recently that PLTP-mediated transfers of phospholipids between HDL and other lipoprotein classes are not interchangeable with the phospholipid transfers that are mediated by cholesteryl ester transfer protein (CETP) (14).The mechanism of the remodeling of HDL by PLTP is poorly understood. Although there is evidence that particle fusion and the dissociation of lipid-poor or lipid-free apoA-I are involved (7,8), nothing is known about how the interaction of PLTP wi...

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Section: H (Closed Triangles)mentioning

confidence: 85%

“…It also remodels HDL into large and small particles in a process that is accompanied by the dissociation of lipid-poor or lipid-free apolipoprotein A-I (apoA-I) (3)(4)(5)(6)(7)(8). Remodeling is enhanced markedly in HDL that contain triglyceride (TG) in their core (9).…”

Section: Phospholipid Transfer Protein (Pltp)mentioning

confidence: 99%

The Mechanism of the Remodeling of High Density Lipoproteins by Phospholipid Transfer Protein

Settasatian¹,

Duong²,

Curtiss³

et al. 2001

Journal of Biological Chemistry

114

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“…The tissue pattern of expression of the HuPLTP gene in transgenic mice more closely resembles the pattern of expression of the endogenous PLTP gene (Figure 3). 33 Compared with plasma of wild-type mice, the plasma of HuPLTP transgenic mice was found to be much more efficient in partially preventing the AcLDL-induced accumulation of intracellular cholesterol in cultured macrophages, in spite of lower levels of total HDL.…”

Section: Discussionmentioning

confidence: 97%

Human Plasma Phospholipid Transfer Protein Increases the Antiatherogenic Potential of High Density Lipoproteins in Transgenic Mice

Haperen

Tol

Vermeulen

et al. 2000

ATVB

185

190

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Abstract-Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress human PLTP were generated. Compared with wild-type mice, these mice show a 2.5-to 4.5-fold increase in PLTP activity in plasma. This results in a 30% to 40% decrease of plasma levels of HDL cholesterol. Incubation of plasma from transgenic animals at 37°C reveals a 2-to 3-fold increase in the formation of pre-␤-HDL compared with plasma from wild-type mice. Although pre-␤-HDL is normally a minor subfraction of HDL, it is known to be a very efficient acceptor of peripheral cell cholesterol and a key mediator in reverse cholesterol transport. Further experiments show that plasma from transgenic animals is much more efficient in preventing the accumulation of intracellular cholesterol in macrophages than plasma from wild-type mice, despite lower total HDL concentrations. It is concluded that PLTP can act as an antiatherogenic factor preventing cellular cholesterol overload by generation of pre-␤-HDL.

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“…1 In vitro, PLTP facilitates the conversion of HDL particles to smaller and larger HDL particle species 2,3 by transferring surface phospholipids between HDL particles leading to particle fusion and displacement of apoA-I from the particles' surface. 4,5 One of the very important PLTP-mediated product HDL particles are the small lipid-poor pre-b-HDL which act as initial acceptors of unesterified cholesterol from cell surfaces. 6,7 CETP catalyzes the transfer of cholesteryl esters (CE) from HDL to apoB-containg lipoproteins in exchange for triglycerides 8,9 resulting in the conversion of larger to smaller particles and low HDL cholesterol levels.…”

Section: Introductionmentioning

confidence: 99%

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

et al. 2001

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AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones -the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration -measured by exogenous substrate assay and enzyme-linked immunosorbent assay -were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

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Functional expression of human and mouse plasma phospholipid transfer protein: effect of recombinant and plasma PLTP on HDL subspecies

Cited by 126 publications

References 21 publications

The Mechanism of the Remodeling of High Density Lipoproteins by Phospholipid Transfer Protein

The Mechanism of the Remodeling of High Density Lipoproteins by Phospholipid Transfer Protein

Human Plasma Phospholipid Transfer Protein Increases the Antiatherogenic Potential of High Density Lipoproteins in Transgenic Mice

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

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