Lovastatin Increases Surface Low Density Lipoprotein Receptor Expression by Retarding the Receptor Internalization Rate in Proliferating Lymphocytes

Abstract

We examined the effects of Lovastatin on LDL receptor (LDL-R) expression and rate of internalization in interleukin-2 (IL-2) expanded phytohemagglutinin-stimulated lymphocytes. Lovastatin increased the surface LDL-R expression, but not DiI-LDL uptake, by up to 30% regardless of whether cell proliferation was affected. It caused a dose-dependent reduction in the LDL-R internalization rate as determined with monensin. Lovastatin had no effect on IL-2 receptor internalization. Inhibition of DNA synthesis by hydroxyurea or protein tyrosine kinase activity by genistein failed to affect the LDL-R internalization rate. Co-incubation of cells with Lovastatin and mevalonate or LDL completely restored the rate of LDL-R internalization. We conclude that Lovastatin increases the apparent surface LDL-R expression by retarding the rate of LDL-R internalization. The effect is mediated through the mevalonate pathway but not the anti-mitogenic property of Lovastatin.