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 alterations of astroglial cells following the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is a key enzyme in cholesterol synthesis. In our previous investigations, it has been demonstrated that lovastatin, which is a specific competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, effectively inhibited cholesterol synthesis in human primary and immortal astrocytes in serum and lipid-free media, and we also showed that the effects on both astrocytes of primary cultures and immortal astrocytes (ASCh-7) were very similar. In the present study we therefore examined effects of lovastatin at a concentration of 100 ng/ml on human immortal astrocytes (ASCh-7) using electron microscopic analysis. We have found that lovastatin significantly affects human immortal astrocytes, resulting 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 screening drugs in pharmacological research but can also provide a useful model for examining fine structural alterations of cells following selective disturbances of metabolism.
Bobryshev
Y V
YV
Institute of the Human Brain, St Petersburg, Russia.
Pavlov
O V
OV
Balabanov
Y V
YV
Ashwell
K
K
D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors*; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008854:Microscopy, Electron
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D008148:Lovastatin