Cholesterol esterification plays a major role in determining low-density-lipoprotein receptor activity in primary monolayer cultures of rat hepatocytes.

A M Salter, N Ekins, M al-Seeni, D N Brindley, B Middleton

Index: Biochem. J. 263(1) , 255-60, (1989)

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Abstract

1. We have previously shown that the capacity for specific binding of human 125I-labelled low-density lipoprotein (LDL) to rat hepatocytes increases with time in culture [Salter, Bugaut, Saxton, Fisher & Brindley (1987) Biochem. J. 247, 79-84]. 2. In the present study we show that this up-regulation is accompanied by a rise in the cholesterol ester content of the cells. 3. Inhibition of cholesterol esterification with the drug 58-035 (Sandoz) significantly decreases the time-dependent 'up-regulation' of LDL receptors. 4. Incubation of hepatocytes with LDL itself has little effect on subsequent LDL binding. However, when cholesterol esterification is inhibited, incubation with LDL decreases binding below that attained with the drug alone. 5. Inhibition of cholesterol synthesis with Lovastatin significantly increases LDL binding and antagonizes the effect of 58-035. 6. We conclude that in hepatocytes the rate of cellular cholesterol esterification can become the major determinant of LDL-receptor activity.