Regulation of low density lipoprotein receptor activity in primary cultures of human hepatocytes by serum lipoproteins

Authors

  • Louis M. Havekes Ph.D.,

    Corresponding author
    1. TNO Gaubius Institute for Cardiovascular Research, Herenstraat 5d, 2313 AD Leiden, The Netherlands
    2. Division of Gastrointestinal and Liver Disease, Department of Medicine, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
    • Gaubius Institute TNO, Herenstraat 5d, 2313 AD Leiden, The Netherlands
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  • Hans Verboom,

    1. TNO Gaubius Institute for Cardiovascular Research, Herenstraat 5d, 2313 AD Leiden, The Netherlands
    2. Division of Gastrointestinal and Liver Disease, Department of Medicine, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
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  • Elly de Wit,

    1. TNO Gaubius Institute for Cardiovascular Research, Herenstraat 5d, 2313 AD Leiden, The Netherlands
    2. Division of Gastrointestinal and Liver Disease, Department of Medicine, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
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  • Sing Hiem Yap,

    1. TNO Gaubius Institute for Cardiovascular Research, Herenstraat 5d, 2313 AD Leiden, The Netherlands
    2. Division of Gastrointestinal and Liver Disease, Department of Medicine, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
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  • Hans M. G. Princen

    1. TNO Gaubius Institute for Cardiovascular Research, Herenstraat 5d, 2313 AD Leiden, The Netherlands
    2. Division of Gastrointestinal and Liver Disease, Department of Medicine, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
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Abstract

The low density lipoprotein receptor activity was measured in primary cultures of human hepatocytes. The receptor-mediated association and degradation of low density lipoprotein increased gradually up to 140 and 190%, respectively, upon incubation of the cells with increasing amounts of whole serum (up to 100%). Preincubation of the cells with low density lipoprotein resulted in a weak downregulation of the receptor-mediated association of low density lipoprotein (only 35% reduction at 100 μg low density lipoprotein per ml). However, preincubation with high density lipoproteins with density between 1.16 and 1.20 gm per ml (heavy high density lipoprotein) resulted in a more than 2-fold stimulation of the receptor-mediated association of low density lipoprotein. This heavy high density lipoprotein-mediated stimulation could not be antagonized by a simultaneous addition of low density lipoprotein during that preincubation.

We conclude that, in primary cultures of human hepatocytes, the downregulation of the low density lipoprotein receptor activity by low density lipoprotein is weak and completely overruled by heavy high density lipoprotein. If these results for human hepatocytes in vitro hold true for hepatocytes in vivo, our results might explain why in vivo liver cells still display low density lipoprotein receptor activity notwithstanding the exposure of these cells to physiological concentrations of low density lipoprotein.

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