STRUCTURAL ALTERATIONS OF HUMAN IMMORTAL ASTROCYTES AFTER INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A (HMG-COA) REDUCTASE BY LOVASTATIN

This investigation was designed to study the specific structural alter ations of astroglial cells following the inhibition of 3-hydroxy-3-met hylglutaryl coenzyme A (HMG-CoA) reductase, which is a key enzyme in c holesterol synthesis. In our previous investigations, it has been demo nstrated that lovastatin, which is a specific competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectivel y inhibited cholesterol synthesis in human primary and immortal astroc ytes in serum and lipid-free media, and we also showed that the effect s on both astrocytes of primary cultures and immortal astrocytes (ASCh -7) were very similar. In the present study we therefore examined effe cts of lovastatin at a concentration of 100 ng/ml on human immortal as trocytes (ASCh-7) using electron microscopic analysis. We have found t hat lovastatin significantly affects human immortal astrocytes, result ing in degenerative ultrastructural changes including accumulation of a large number of phagosomes, oedema of the cytoplasm and destruction of gliofilaments. The results obtained suggest that the human immortal astrocyte cell line (ASCh-7) can be not only very useful for screenin g drugs in pharmacological research but can also provide a useful mode l for examining fine structural alterations of cells following selecti ve disturbances of metabolism.