Regulation of Low Density Lipoprotein Receptor Function in a Human Hepatoma Cell Line

✍ Scribed by Alan M. Leichtner; Monty Krieger; Alan L. Schwartz

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 599 KB
• Volume: 4
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840040638

✦ Synopsis

Low density lipoprotein (LDL) processing was investigated in a human hepatoma-derived cell line, Hep G2. Hep G2 cells bound, internalized and degraded LDL via a saturable, high affinity (Kd -2 x lo-' M ) pathway similar to that present in other mammalian cells. Although 80% of the uptake and degradation of "'I-LDL was inhibited by 40-fold excess native LDL, the same concentration of methylated LDL, which cannot bind to LDL receptors, had virtually no effect on processing. When added at low concentrations, the lysosomotropic agent, chloroquine, inhibited degradation (I6,, -15 p M ) without affecting the rate of lipoprotein internalization. Receptor activity was decreased 60% by preincubation of the cells in medium containing a source of cholesterol (LDL or unesterified cholesterol) and increased 1.7-fold by preincubation with compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The Hep 6 2 cell line may prove a useful system both for the further study of hepatic lipoprotein metabolism and for the evaluation of new antihypercholesterolemic agents.