Effect of serum lipoproteins on growth and sterol synthesis in cultured rat brain glial cells.
Cells dissociated from brains of 1-day-old rats were cultured in medium containing either lipoprotein-deficient serum (LPDS) or LPDS plus various lipoprotein fractions. Increases in number of cells and in DNA content served as a measure of cell growth. Cholesterol synthesis was measured from the incorporation of [14C]acetate into total nonsaponifiable lipids and digitonin-precipitable sterols, and from the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. The data indicated that cholesterol biosynthesis from acetate was reduced in cells cultured in medium containing either LPDS plus low-density lipoproteins (LDL), high-density lipoproteins (HDL), or total lipoproteins (LP) and that this reduction was accompanied by a reduction in the activity of the HMG CoA reductase and an increase in the esterified sterol content. The reduction in cholesterol synthesis from acetate was maximal in cells cultured in the presence of HDL, whereas the maximal reduction in the activity of HMG CoA reductase occurred in cells cultured in the presence of LP. The presence of LDL or LP in the culture medium enhanced the cell growth but the presence of HDL did not. Esterified sterol content was highest in cells cultured in the medium containing LPDS plus LP and was not detected in cells cultured in LPDS medium. It is inferred from these data that rat brain glial cells in culture are able to utilize cholesterol in lipoproteins, that the presence of LDL in the medium enhances cell growth, and that reduced cholesterol synthesis in the presence of lipoproteins may occur at the HMG CoA reductase step as well as at some other step(s).
Shah
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SN
Department of Psychiatry, University of California, Eldridge 95431.
Johnson
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RC
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D001769:Blood; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013261:Sterols / Q000096:biosynthesis*
D000085:Acetates; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D013261:Sterols; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D019342:Acetic Acid