Induction of intracellular acyl-CoA:cholesterol acyltransferase activity in glioblastoma cells by lidocaine.
The perturbation of cellular cholesteryl ester biosynthesis in glioblastoma C-6 cells by lidocaine was investigated. Lidocaine specifically inhibited the incorporation of radioactive oleic acid into cellular cholesteryl ester but had no significant effect on the incorporation of oleic acid into phosphatidylcholine. Oxygenated cholesterol-enhanced cholesteryl ester formation was less sensitive to lidocaine inhibition. Several other local anesthetics were compared. Lidocaine altered cholesteryl ester formation in time- and dose-dependent manners. Lidocaine was a powerful inhibitor initially and its potency declined with time. Lidocaine was capable of directly inhibiting acyl-CoA:cholesterol acyltransferase (ACAT) activity in broken cell homogenates. The lidocaine-mediated inhibition of cellular cholesteryl ester formation triggered an enhanced intracellular ACAT activity that was not fully expressed in the presence of lidocaine. The activation of ACAT activity by lidocaine might represent a compensatory mechanism by which the inhibitory effect of lidocaine was partially overcome with time.
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005910:Glioma; D008012:Lidocaine / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000096:biosynthesis*; D013997:Time Factors
D000779:Anesthetics, Local; D002788:Cholesterol Esters; D009829:Oleic Acids; D010713:Phosphatidylcholines; D019301:Oleic Acid; D008012:Lidocaine; D002785:Sterol O-Acyltransferase