Original Article

Lipids

, Volume 46, Issue 4, pp 323-332

First online:

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

  • Shin-ya MoritaAffiliated withKobe Pharmaceutical University Email author 
  • , Atsushi SakuraiAffiliated withGraduate School of Pharmaceutical Sciences, Kyoto University
  • , Minoru NakanoAffiliated withGraduate School of Pharmaceutical Sciences, Kyoto University
  • , Shuji KitagawaAffiliated withKobe Pharmaceutical University
  • , Tetsurou HandaAffiliated withGraduate School of Pharmaceutical Sciences, Kyoto UniversityFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science

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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.

Keywords

Apolipoprotein C-III Apolipoprotein E Cholesterol Lipid emulsions