Induction of low-density lipoprotein catabolism in Hep G2 cells by a fungal sesquiterpene ester, FR111142.
A search for agents that can enhance low density lipoprotein (LDL) catabolism in Hep G2 cells has led to the identification of a fungal sesquiterpene ester, FR111142, as an active compound. The treatment of Hep G2 cells with 40 microM FR111142 at 37 degrees C for 18 h caused a 1.9- to 2.2-fold elevation of binding, internalization and degradation of 125I-LDL in the cells. The Scatchard analysis of the specific 125I-LDL binding demonstrated that the agent caused an increase in the maximum LDL binding along with a slight decrease in the apparent dissociation constant value. The effect of FR111142 was not seen in cells treated by the agent for shorter periods or in cycloheximide-treated cells, suggesting that the effect involves an induction of LDL binding sites. Unlike 3-hydroxy-3-methyglutaryl CoA reductase inhibitors, FR111142 affected neither cholesterol synthesis nor the level of LDL receptor in Hep G2 cells. These results suggest that FR111142 enhances LDL catabolism in Hep G2 cells by a mechanism that involves a receptor other than LDL receptor.
Harada
T
T
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Tokyo, 183-8509, Japan.
Hasumi
K
K
Endo
A
A
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology*; D005658:Fungi / Q000737:chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D013261:Sterols / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000924:Anticholesteremic Agents; D004852:Epoxy Compounds; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D012717:Sesquiterpenes; D013141:Spiro Compounds; D013261:Sterols; C074363:FR 111142; C012258:mevastatin; D008148:Lovastatin