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Presence of Apolipoprotein C-III Attenuates Apolipoprotein E-Mediated Cellular Uptake of Cholesterol-Containing Lipid Particles by HepG2 Cells

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Lipids

Abstract

Apolipoprotein C-III (apoC-III) decreases the apolipoprotein E (apoE)-mediated uptake of lipoprotein remnants by the liver, and a high plasma concentration of apoC-III in VLDL is associated with hypertriglyceridemia and the risk of coronary heart disease. In this study, we prepared lipid emulsions containing triolein, phosphatidylcholine and cholesterol as model particles of lipoproteins, and examined the roles of apoC-III in apoE-mediated uptake of emulsions by HepG2 cells. Cholesterol in emulsion particles enhanced the apoE-mediated uptake via heparan sulfate proteoglycan and LDL receptor-related protein pathways. The amount of apoE bound to emulsion particles was increased by the presence of cholesterol at the particle surface, whereas cholesterol had no effect on the binding amount of apoC-III. Surface cholesterol alleviated the inhibitory effect of apoC-III on apoE incorporation into the emulsion surface. However, ApoC-III almost completely inhibited the apoE-mediated uptake of cholesterol-containing emulsions despite sufficient binding of apoE to emulsions. These findings suggest that apoC-III attenuates the binding of apoE to the lipoprotein surface and apoE-mediated cellular uptake of lipoprotein remnants. Furthermore, cholesterol may affect these functions of apoC-III and apoE involved in the clearance of lipoprotein remnants.

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Abbreviations

apoC-III:

Apolipoprotein C-III

apoE:

Apolipoprotein E

HSPG:

Heparan sulfate proteoglycan

LRP:

LDL receptor-related protein

PL:

Phospholipid

PMC oleate:

Pyrenemethyl 3β-(cis-9-octadecenoyloxy)-22,23-bisnor-5-cholenate

PtdCho:

Phosphatidylcholine

TAG:

Triacylglycerol

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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research and Young Scientists from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (17390011 and 22790053), by the Program for the Promotion of Fundamental Studies in Health Science (04-8) of the National Institute of Biomedical Innovation (NIBIO), and a grant from Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

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  1. Tetsurou Handa

    Present address: Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minami-Tamagaki-cho, Suzuka, Mie, 513-8670, Japan

Authors and Affiliations

  1. Kobe Pharmaceutical University, Higashinada-ku, Kobe, 658-8558, Japan

    Shin-ya Morita & Shuji Kitagawa

  2. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Atsushi Sakurai, Minoru Nakano & Tetsurou Handa

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  1. Shin-ya Morita
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  2. Atsushi Sakurai
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  3. Minoru Nakano
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Correspondence to Shin-ya Morita.

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Morita, Sy., Sakurai, A., Nakano, M. et al. Presence of Apolipoprotein C-III Attenuates Apolipoprotein E-Mediated Cellular Uptake of Cholesterol-Containing Lipid Particles by HepG2 Cells. Lipids 46, 323–332 (2011). https://doi.org/10.1007/s11745-010-3498-9

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