Effects of F-1394, an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity in HepG2 cells and on hepatic secretion of lipids in Triton WR-1339-induced hyperlipidemic rats: Possible role of hepatic ACAT in very low density lipoprotein secretion

Japanese Journal of Pharmacology

Volumn 76, Issue 3, 1998, Pages 309-312

  Aragane, Katsumi ^a   Kusunoki, Jun ^a   Kitamine, Tetsuya ^a   Yamaura, Tetsuaki ^a   Ohnishi, Haruo ^a  

^a FUJIREBIO INC   (Japan)

Author keywords

Acyl CoA:cholesterol acyltransferase; F 1394; Triton WR 1339

Indexed keywords

1,3 BIS[[1 CYCLOHEPTYL 3 (4 DIMETHYLAMINOPHENYL)UREIDO]METHYL]BENZENE; 2 [3 (2,2 DIMETHYLPROPYL) 3 NONYLUREIDO]CYCLOHEXANE 1 YL 3 [N (2,2,5,5 TETRAMETHYL 1,3 DIOXANE 4 CARBONYL)AMINO]PROPIONIC ACID; 2,2 DIMETHYL N (2,4,6 TRIMETHOXYPHENYL)DODECANAMIDE; 3 (2,4 DIFLUOROPHENYL) 1 HEPTYL 1 (4 NEOPENTYLBENZYL)UREA; 57 118; ANTILIPEMIC AGENT; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; LIPID; MELINAMIDE; TRIACYLGLYCEROL; TYLOXAPOL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL STRAIN HEPG2; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOSE RESPONSE; DRUG POTENCY; ENZYME ACTIVITY; ENZYME INHIBITION; HYPERLIPIDEMIA; LIVER; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; TRIACYLGLYCEROL BLOOD LEVEL;

EID: 0031948269     PISSN: 00215198     EISSN: None     Source Type: Journal    
DOI: 10.1254/jjp.76.309     Document Type: Article

References (15)

1. Sliskovic DR and White AD: Therapeutic potential of ACAT inhibitors as lipid lowering and anti-atherosclerotic agents. Trends Pharmacol Sci 12, 194-199 (1991)
2. Kusunoki J, Aragane K, Yamaura T and Ohnishi H: Studies on acyl-CoA:cholesterol acyltransferase (ACAT) inhibitory effects and enzyme selectivity of F-1394, a pantotheic acid derivative. Jpn J Pharmacol 67, 195-203 (1995)
3. Kusunoki J, Aragane K, Kitamine T, Higashinakagawa S, Kase N, Yamaura T and Ohnishi H: Hypocholesterolemic action and prevention of cholesterol absorption via the gut by F-1394, a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in cholesterol diet-fed rats. Jpn J Pharmacol 69, 53-60 (1995)
4. Kusunoki J, Aragane K, Kitamine T, Yamaura T and Ohnishi H: Hypolipidemic action of F-1394, an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in high fat diet-fed beagle dogs. Yakugakuzasshi 117, 233-241 (1997) (Abstr in English)
5. Borenztajn J, Roune MS and Kotlar TJ: The inhibition in vivo of lipoprotein lipase (clearing-factor lipase) activity by Triton WR-1339. Biochem J 156, 539-543 (1976)
6. Norum KR, Helgerud P and Lilljeqvist A-C: Enzymatic esterification of cholesterol in rat intestinal mucosa catalyzed by acyl-CoA:cholesterol acyltransferase. Scand J Gastroenterol 16, 401-410 (1981)
7. Drevon CA, Engelhorn SC and Steinberg D: Secretion of very low density lipoproteins enriched in cholesteryl esters by cultured rat hepatocytes during stimulation of intracellular cholesterol esterification. J Lipid Res 21, 1065-1071 (1980)
8. Cianflone KM, Yasruel Z, Rodriguez MA, Vas D and Sniderman AD: Regulation of apoB secretion from HepG2 cells: evidence for a critical role for cholesteryl ester synthesis in the response to a fatty acid challenge. J Lipid Res 31, 2045 -2055 (1990)
9. Largis EE, Wang CH, DeVries VG and Schaffer SA: CL-277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. J Lipid Res 30, 681-690 (1989)
10. Schnitzer-Polokoff R, Compton D, Boykow G, Davis H and Burner R: Effects of acyl-CoA:cholesterol acyltransferase inhibition on cholesterol absorption and plasma lipoprotein composition in hamsters. Comp Biochem Physiol 99A, 665-670 (1991)
11. Marzetta CA, Savoy YE, Freeman AM, Long CA, Pettini JL, Hagar RE, Inskeep PB, Davis K, Stucchi AF, Nicolosi RJ and Hamanaka ES: Pharmacological properties of a novel ACAT inhibitor (CP-113,818) in cholesterol-fed rats, hamsters, rabbits, and monkeys. J Lipid Res 35, 1829-1838 (1994)
12. Strobl W, Gorder NL, Fienup GA, Lin-Lee Y, Gotto AM and Patsh W: Effect of sucrose diet on apolipoprotein biosynthesis in rat liver. Increase in apolipoprotein E gene transcription. J Biol Chem 264, 1190-1194 (1989)
13. Krause BR, Anderson M, Bisgaier CL, Bocan T, Bousley R, DeHart P, Essenburg A, Hamelehle K, Homan R, Kieft K, McNally W, Stanfield R and Newton RS: In vivo evidence that the lipid-regulating activity of the ACAT inhibitor CI-976 in rats is due to inhibition of both intestinal and liver ACAT. J Lipid Res 34, 279-294 (1993)
14. Graham A, Wood JL and Russell LJ: Cholesterol esterification is not essential for secretion of lipoprotein components by HepG2 cells. Biochim Biophys Acta 1302, 46-54 (1996)
15. Wu X, Sakata N, Lui E and Ginsberg HN: Evidence for a lack of regulation of the assembly and secretion of apolipoprotein B-containing lipoprotein from HepG2 cells by cholesteryl ester. J Biol Chem 269, 12375-12382 (1994)