LOVASTATIN INCREASES SURFACE LOW-DENSITY-LIPOPROTEIN RECEPTOR EXPRESSION BY RETARDING THE RECEPTOR INTERNALIZATION RATE IN PROLIFERATING LYMPHOCYTES

We examined the effects of Lovastatin on LDL receptor (LDL-R) expressi on and rate of internalization in interleukin-2 (IL-2) expanded phytoh emagglutinin-stimulated lymphocytes. Lovastatin increased the surface LDL-R expression, but not DiI-LDL uptake, by up to 30% regardless of w hether cell proliferation was affected. It caused a dose-dependent red uction 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-incubat ion of cells with Lovastatin and mevalonate or LDL completely restored the rate of LDL-R internalization. We conclude that Lovastatin increa ses the apparent surface LDL-R expression by retarding the rate of LDL R internalization. The effect is mediated through the mevalonate pathw ay but not the anti-mitogenic property of Lovastatin. (C) 1997 Academi c Press.