Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo

Journal of Lipid Research

Volumn 38, Issue 3, 1997, Pages 564-575

  Eisele, Bernhard ^a   Budzinski, Ralph ^a   Müller, Peter ^a   Maier, Roland ^a   Mark, Michael ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

2,3 monoepoxysqualene; 2,3:22,23 diepoxysqualene; HMG CoA reductase; lanosterol; LDL kinetics; oxysterols; squalene oxidase; VLDL secretion

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; LANOSTEROL SYNTHASE; SIMVASTATIN;

ARTICLE; CATABOLISM; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; CYCLIZATION; DRUG EFFECT; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYPERLIPIDEMIA; IN VIVO STUDY; LIPID METABOLISM; LIPOPROTEIN SECRETION; LIPOPROTEIN SYNTHESIS; PRIORITY JOURNAL; RECEPTOR UPREGULATION;

ANIMALS; CHOLESTEROL; CRICETINAE; ENZYME INHIBITORS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; INTRAMOLECULAR TRANSFERASES; ISOMERASES; LIPID METABOLISM; LIPIDS; LIPOPROTEINS, LDL; LIVER; MALE; MESOCRICETUS; MICE; MICE, INBRED STRAINS; OXAZOLES; PIPERIDINES; RATS; RATS, WISTAR; RECEPTORS, LDL; RNA, MESSENGER; SQUALENE; TUMOR CELLS, CULTURED;

EID: 0030951557     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (35)

1. Alberts, A. W. 1990. Lovastatin and simvastatin - inhibitors of HMG-CoA reductase and cholesterol biosynthesis. Cardiology. 77: 14-21.
2. Endo, A. 1985. Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J. Biol. Chem. 28: 401-405.
3. Malmendier, C. L., J. F. Lontie, C. Delcroix, and T. Magot. 1989. Effect of simvastatin on receptor-dependent low density lipoprotein catabolism in normocholesterolemic human volunteers. Atherosclerosis. 80: 101-109.
4. Gaw, A., C. J. Packard, E. F. Murray, G. M. Lindsay, B. A. Griffin, M. J. Caslake, B. D. Vallance, A. R. Lorimer, and J. Shepherd. 1993. Effects of simvastatin an apoB metabolism and LDL subfraction distribution. Arterioscler. Thromb. 13: 170-189.
5. Ma, P. T., G. Gil, T. C. Sudhof, D. W. Bilheimer, J. L. Goidstein, and M. S. Brown. 1986. Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc. Natl. Acad. Sci. USA. 83: 8370-8374.
6. Matsunaga, A., J. Sasaki, Y. Takada, K. Hidaka, and K. Arakawa. 1991. Effect of simvastatin on receptor-mediated metabolism of low density lipoprotein in guinea pigs. Atherosclerosis. 90: 31-37.
7. Goldberg, I. J., S. Holleran, R. Ramakrishan, M. Adams, R. H. Palmer, R. B. Dell, and D. S. Goodman. 1990. Lack of effect of lovastatin therapy on the parameters of whole-body cholesterol metabolism. J. Clin. Invest. 86: 801-808.
8. Brown, M. S., J. R. Faust, L. Goldstein, I. Kaneko, and A. Endo. 1978. Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. J. Biol. Chem. 253: 1121-1128.
9. Endo, A., Y. Tsujita, M. Kuroda, and K. Tanzawa. 1979. Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals. Biochim. Biophys. Acta. 575: 266-276.
10. Cohen, L. H., A. van Vliet, L. Roodenburg, L. M. Jansen, and M. Griffioen. 1993. Pravastatin inhibited the cholesterol synthesis in human hepatoma cell line Hep G2 less than simvastatin and lovastatin, which is reflected in the up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and squalene synthase. Biochem. Pharmacol. 45: 2203-2208.
11. Fujioka, T., F. Nara, Y. J. Tsujita, Fukushige, M. Fukami, and M. Kuroda. 1995. The mechanism of lack of hypocholesterolemic effects of pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rats. Biochim. Biophys. Acta. 1254: 7-12.
12. Qin, W., J. Infante, S. R. Wang, and R. Infante. 1992. Regulation of HMG-CoA reductase, apoprotein-B and LDL receptor gene expression by the hypocholesterolemic drugs simvastatin and ciprofibrate in HepG2, human and rat hepatocytes. Biochim. Biophys. Acta. 1127: 57-66.
13. Mark, M., P. Müller, R. Maier, and B. Eisele. 1996. Effects of a novel 2,3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells. J. Lipid Res. 37: 148-158.
14. Saucier, S. E., A. A. Kandutsch, F. R. Taylor, T. A. Spencer, S. Phirwa, and A. K. Gayen. 1985. Identification of regulatory oxysterols, 24(S),25-epoxycholesterol and 25-hydroxycholesterol, in cultured fibroblasts. J. Biol. Chem. 260: 14571-14579.
15. Panini, S. R., R. C. Sexton, and H. Rudney. 1984. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by oxysterol by-products of cholesterol biosynthesis. Possible mediators of low density lipoprotein action. J. Biol. Chem. 259: 7767-7771.
16. Panini, S. R., T. A. Delate, and M. Sinensky. 1992. Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 24(S),25-oxidolanosterol. J. Biol. Chem. 267: 12647-12654.
17. Bai, M., X. Xiao, and G. D. Prestwich. 1992. Epoxidation of 2,3-oxidosqualene to 2,3;22,23-squalene dioxide by squalene epoxidase. Biochem. Biophys. Res. Commun. 185: 323-329.
18. Abe, I., and G. D. Prestwich. 1995. Identification of the active site of vertebrate oxidosqualene cyclase. Lipids. 30: 231-234.
19. Bligh, E. G., and W. J. Dyer. 1959. A rapid method of total lipid extraction and purification Can. J. Biochem. Physiol. 37: 911-917.
20. Lowry, O. H., N.J. Rosebrough, A. L. Farr, and R. J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265-275.
21. Turley, S. D., B. P. Daggy, and J. M. Dietschy. 1991. Cholesterol-lowering action of psyllium mucilloid in the hamster: sites and possible mechanisms of action. Metabolism. 40: 1063-1073.
22. Eisele, B., S. R. Bates, and R. W. Wissler. 1980. Interaction of low density lipoproteins from normal and hyperlipemic rhesus monkeys with arterial smooth muscle cells in culture. Atherosclerosis. 36: 9-24.
23. Heinzel, G., R. Woloszczak, and P. Thomann. 1993. Top-Fit Version 2.0, Pharmacokinetic and pharmacodynamic data analysis system for the PC. Gustav Fischer Verlag Stuttgart, Jena, New York ISBN 3-347-11486-7 (Stuttgart) ISBN 1-56081-368 (New York).
24. Chomczynski, P., and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156-159.
25. Joint Working Group on Refinement. 1993. Removal of blood from laboratory mammals and birds. Lab. Anim. 27: 1-22.
26. Dollis, D., and F. Schuber. 1994. Effects of a 2,3-oxido-squalene-lanosterol cyclase inhibitor, 2,3:22,23-dioxido-squalene and 24,25-epoxycholesterol on the regulation of cholesterol biosynthesis in human hepatoma cell line HepG2. Biochem. Pharmacol. 48: 49-57.
27. Otway, S., and D. S. Robinson. 1967. The use of a non-ionic detergent to determine the rates of triglyceride entry into the circulation of the rat under different physiological conditions. J. Physiol. 190: 321-332.
28. Otway, S., and D. S. Robinsion. 1967. The effect of a non-ionic detergent on the removal of triglyceride fatty acids from the blood of the rat. J. Physiol. 190: 309-319.
29. Khan, B. V., T. J. Fungwe, H. G. Wilcox, and M. Heimberg. 1990. Cholesterol is required for the secretion of very low density lipoprotein: in vivo studies. Biochim. Biophys. Acta. 1044: 297-304.
30. Arbeeny, C. M., D. S. Meyers, K. E. Bergquist, and R. E. Gregg. 1992. Inhibition of fatty acid biosynthesis decreases very low density lipoprotein secretion in the hamster. J. Lipid Res. 33: 834-851.
31. Kasim, S. E., J. Elovson, S. Khilnanai, R. U. Almario, and K. L. C. Jen. 1993. Effect of lovastatin on the secretion of lipoprotein lipids and apolipoprotein B in the hypertriglyceremic Zucker obese rat. Atherosclerosis. 104. 147-152.
32. Goldstein, J. L., and M. S. Brown. 1990. Regulation of the mevalonate pathway. Nature. 343: 425-430.
33. Groot, P. H. E., N. J. Pearce, K. E. Suckling, and S. Eisenberg. 1992. Effects of cholestyramine on lipoprotein levels and metabolism in Syrian hamsters. Biochim. Biophys. Acta. 1123: 76-84.
34. Meddings J. B., and J. M. Dietschy. 1986. Regulation of plasma levels of low-density lipoprotein cholesterol: interpretation of data on low-density lipoprotein turnover in man. Circulation. 74: 805-814.
35. Panini, S. R., G. T. Everson, and T. A. Spencer. 1991. Effect of specific inhibition of sterol biosynthesis on the uptake and utilization of low density lipoprotein cholesterol by HepG2 cells. J. Lipid Res. 32: 1657-1665.