Complete down-regulation of low-density lipoprotein receptor activity in human liver parenchymal cells by beta-very-low-density lipoprotein

The effect of LDL and beta-VLDL on the expression of the LDL receptor is studied in cultured human parenchymal cells. The high affinity binding of [125I]LDL to cultured human parenchymal cells was down regulated to 37.3 +/- 2.9% and 24.0 +/- 2.6% of the control value, after preincubation with LDL or beta-VLDL for 22 h, respectively. When LDL receptor synthesis was blocked at 22 h a residual receptor activity of 29% is noticed, indicating a half-life of LDL receptors in human parenchymal cells of 12 h. It is concluded that LDL receptor expression on human liver parenchymal cells is subject to complete down-regulation by beta-VLDL, which may be held responsible for the cholesterol-rich diet induced down-regulation of LDL receptors, in vivo.