Pharmacological inhibition of the intracellular transport of low-density lipoprotein-derived cholesterol in Chinese hamster ovary cells.
Mammalian cells, cultured in the presence of serum lipoproteins, acquire cholesterol necessary for growth from the uptake and lysosomal hydrolysis of low-density lipoproteins (LDL). The mechanism(s) of intracellular transport of LDL-derived cholesterol from lysosomes to other cellular sites is unknown. In this study, various pharmacological agents were assessed for their ability to inhibit the movement of LDL-cholesterol from lysosomes to the plasma membrane. The only pharmacological agent tested in these experiments that specifically inhibited LDL-cholesterol movement was U18666A. Ketoconazole impaired the intracellular transport of LDL-cholesterol; however, ketoconazole also had a general effect on cholesterol movement, since it impeded the desorption of endogenously synthesized cholesterol into the medium. Other drugs that affected cholesterol movement appeared to be nonspecific. Cholesterol transport from lysosomes to plasma membranes was not significantly altered by agents that affect lysosomal function or cytoskeletal organization, as well as energy poisons and cycloheximide.
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Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology; D007700:Kinetics; D008985:Monensin / Q000494:pharmacology; D010053:Ovary
D000736:Androstenes; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D008985:Monensin; D002784:Cholesterol; D007654:Ketoconazole