Cyclic AMP decreases LDL catabolism and cholesterol synthesis in the human hepatoma cell line HepG2.
A 24h pretreatment of the human hepatoma cell line HepG2 with dibutyryl cyclic AMP in the presence of theophylline induced a dose dependent decrease in low density lipoprotein binding, uptake and degradation. This effect is most likely due to a reduction of the LDL receptor number. Sterol synthesis from sodium acetate is markedly inhibited, either in the presence or absence of LDL, whereas synthesis from mevalonic acid is unchanged. Cyclic AMP also induced a decrease in hydroxy methyl glutaryl coenzyme A reductase activity. These effects of cyclic AMP might be involved in some hormonal regulation of the LDL pathway and cholesterol metabolism in the liver.
Maziere
C
C
Faculté de Médecine Saint-Antoine, Paris, France.
Maziere
J C
JC
Salmon
S
S
Auclair
M
M
Mora
L
L
Moreau
M
M
Polonovski
J
J
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D003994:Bucladesine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D000085:Acetates; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D003994:Bucladesine; D002784:Cholesterol; D013806:Theophylline; D000242:Cyclic AMP; D006903:Hydroxymethylglutaryl CoA Reductases; D019342:Acetic Acid; D008798:Mevalonic Acid