ROLE FOR MICROTUBULES IN THE REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE AND CHOLESTEROL-BIOSYNTHESIS IN CULTURED GLIAL-CELLS

—Cultured C‐6 glial cells were utilized to evaluate the effect of the antimicrotubular drug, Colcemid, on 3‐hydroxy‐3‐melhylglutaryl coenzyme A (HMG‐CoA) reductase and cholesterol synthesis in cultured C‐6 glial cells. The data indicate that Colcemid causes a marked inhibition of cholesterol synthesis (from [14C]acetate or 3H2O) in these cells. A concentration of 0.5 μM led to a 50% lower rate of synthesis after 2 h and an 80–85% lower rate after 12 h or longer. That the effect of Colcemid is mediated at the level of HMG‐CoA reductase was shown by defining closely coordinate temporal and quantitative changes in the activity of this enzyme under identical conditions. No comparable change in cell growth or in total protein synthesis accompanied the effect of Colcemid. The drug did lead to a decrease in the rate of DNA synthesis (from [3H]thymidine) but this effect was preceded by the decrease in the rate of cholesterol synthesis. Marked changes in glial cell shape were induced by exposure to Colcemid, and the temporal and quantitative aspects of these changes appeared to closely parallel the effects on reductase activily and cholesterol synthesis. The dala suggest that microtubules are involved in the regulation of HMG‐CoA reductase and cholesterol synthesis in mammalian cells and that there are important interrelations between microtubules, glial differentiation and cholesterol synthesis. Copyright © 1979, Wiley Blackwell. All rights reserved