Activation of low density lipoprotein receptor synthesis by treatment with partially delipidated low density lipoprotein

The role of apo-low density lipoprotein in the regulation of low density lipoprotein receptor synthesis was studied. Fibroblasts preincubated in the presence of a cholesterol-free low density lipoprotein preparation showed an increase of 50% in receptor activity. In contrast, when cells were preincubated with a similar amount of normal low density lipoproteins a 2- to 3-fold decrease of receptor activity was observed. The increase of receptor activity induced by delipidated LDL was probably due to an increase of synthesis rather than an unmasking effect since treatment with puromycin essentially abrogated the activation. The ability of the partially delipidated low density lipoproteins to elicit receptor synthesis could not be accounted for by a depletion of cellular cholesterol because a similar preparation of delipidated high density lipoproteins was unable to induce receptor synthesis but was able to reduce cellular cholesterol to the same extent. Treatment with chloroquine, a lyzosome inhibitor, blocked the ability of the delipidated low density lipoprotein to activate receptor synthesis. This suggests that degraded fragments rather than the intact delipidated lipoprotein are necessary to trigger the cell to synthesize more receptors.