Studies for Uptake of Serum Cholesterol by Isolated Hepatocytes and Hepatoma cells of Rats In Vitro

Abstract

Uptake of serum cholesterol by isolated hepatocytes and hepatoma cells of rats was investigated in vitro. The uptake of cholesterol by the hepatocytes at 4° was very low and did not increase by the prolongation of the incubation time. However, the amount of cholesterol taken up by the hepatocytes at 37.5° was high and increased proportionally to the incubation time and serum cholesterol concentration. Such mechanism of uptake is not considered to be a nonspecific physiochemical process but a specifi carrier-mediated process. Ester cholesterol in the medium decreased more rapidly than free cholesterol during the incubation, but cholesterol in the hepatocytes was mainly found in the free form, suggesting that ester cholesterol taken up by the cells was hydrolyzed rapidly. Cholesterol in the every serum lipoprotein fractions could be transfered to the hepatocytes in vitro. The uptake of cholesterol diminished in old rats or hypothyroid rats. The isolated hepatocytes from rats hyporesponding to a high cholesterol diet took up more cholesterol than those from the hyperresponders.
The uptakes by the isolated tumor cells (AH 130 and SLC) were very low, about one fifteenth or one twentieth of the hepatocytes, when expressed by per cell number. Purified tumor membranes, however, were as capable of binding the serum cholesterol as hepatocyte membranes. Therefore, the lack of negative feed back control of cholestero-synthesis in malignant cells is not derived from the absence or decrease of binding ability of lipoproteins to cell membranes, but probably from a lower rate of internalization of lipoproteins from surface membrane into cytoplasma.