The reversal of the inhibition on lipids synthesis by L-659,699 in arterial smooth muscle cells cultures.
The beta-lactone isolated from Fusarium sp. termed L-659,699 is a potent specific inhibitor of the enzyme 3-hydroxi-3-methylglutaril coenzyme A (HMG-CoA) synthase. In cultures of smooth muscle cells (SMC) isolated from aortic-arch of control (C-SMC) and 5% of cholesterol diet (Ch-SMC) treated chicks, the incorporation of (14C)-acetate to lipids (cholesterol, triacylglycerides and cholesterol ester) were greater in Ch-SMC cultures than in C-SMC and the presence of 0.05 microM L-659,699 for 2 h in the incubation medium decrease the synthesis of cholesterol however the triacylglycerides synthesis increase. The effect of inhibitor is stronger in young cultures (3-4 steps) than in the older ones (11-12 steps). In young C-SMC and Ch-SMC cultures the inhibition of cholesterol and triacylglycerides synthesis by L-659,699 was reversal.
Carazo
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A
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Spain.
Alejandre
M J
MJ
Louktibi
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Linares
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D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000166:cytology*; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000096:biosynthesis; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors*; D004036:Diet, Atherogenic; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006904:Hydroxymethylglutaryl-CoA Synthase; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis
D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D007783:Lactones; D008055:Lipids; D014280:Triglycerides; C054282:antibiotic 1233A; D002784:Cholesterol; D006904:Hydroxymethylglutaryl-CoA Synthase; D003066:Coenzyme A Ligases