The regulation of sterol metabolism by cell interactions.
Total and free cholesterol levels in C6 glial cells are regulated by a cell interaction-dependent mechanism that operates independently of exogenous cholesterol and serum lipoproteins. This mechanism, which is activated by changes in culture density, coordinately regulates the activities of HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT). Both enzyme activities are low in sparse density cultures, rise as density increases from sparse to moderate, and decrease with further density increases. When culture density is abruptly elevated, both enzyme activities decay rapidly and with biphasic kinetics. Neither enzyme phosphorylation nor diffusible cytosolic factors appear to be directly involved in density suppression of HMG-CoA reductase. Studies with human fibroblasts that are defective in LDL receptor function demonstrate that density regulation does not require a functional LDL receptor. Extracellular matrix and soluble factors have also been ruled out as intercellular mediators. The specific growth rate of C6 cultures changes with density in the same manner as sterol metabolism. The possibility that growth and sterol metabolism are regulated by a common cell interaction-dependent mechanism is discussed.
D000469:Alkaline Phosphatase / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis* / Q000494:pharmacology; D003260:Contact Inhibition; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D005910:Glioma / Q000473:pathology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism*; D010766:Phosphorylation; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D009363:Neoplasm Proteins; D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D000469:Alkaline Phosphatase