Compactin (ML-236B) reduces the content of filipin-cholesterol complexes in the plasma membrane of chronic lymphocytic leukemia cells.
The polyene antibiotic filipin was used to visualize the presence and distribution of cholesterol in the plasma membrane of glutaraldehyde-fixed human chronic lymphocytic leukemia (CLL) cells. Both compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and 25-hydroxycholesterol reduced the content of filipin-cholesterol complexes in the plasma membrane of CLL cells grown in media supplemented with either 15% delipidized horse serum or 15% normal (whole) horse serum. The reduction due to compactin was reversed by the concomitant addition of mevalonolactone. The ability of compactin to reduce the relative cholesterol content (as judged by filipin labeling) in CLL cells grown in lipoprotein-containing (normal) serum suggest that either CLL cells are different from other cells in that they predominantly utilize endogenously synthesized cholesterol for incorporation into the plasma membrane, or that a separate pool of endogenously synthesized cholesterol provides cholesterol for the plasma membrane.
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005372:Filipin / Q000378:metabolism*; D005614:Freeze Fracturing; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000473:pathology / Q000503:physiopathology*; D008148:Lovastatin / Q000031:analogs & derivatives*; D008563:Membrane Lipids / Q000378:metabolism*; D008854:Microscopy, Electron; D009281:Naphthalenes / Q000494:pharmacology*; D011090:Polyenes / Q000378:metabolism*
D000924:Anticholesteremic Agents; D008563:Membrane Lipids; D009281:Naphthalenes; D011090:Polyenes; C012258:mevastatin; D005372:Filipin; D002784:Cholesterol; D008148:Lovastatin