Direct perturbation of lens membrane structure may contribute to cataracts caused by U18666A, an oxidosqualene cyclase inhibitor

Journal of Lipid Research

Volumn 45, Issue 7, 2004, Pages 1232-1241

  Cenedella, Richard J ^a   Jacob, Robert ^b   Borchman, Douglas ^c   Tang, Daxin ^c   Neely, Amanda R ^a   Samadi, Abbas ^a   Mason, R Preston ^b   Sexton, Patricia ^a  

^a A T STILL UNIVERSITY   (United States)

^b ELUCIDA RESEARCH LLC   (United States)

^c University of Louisville School of Medicine   (United States)

Author keywords

Anisotropy; Apoptosis; Cholesterol; Lens membrane lipids; X ray diffraction

Indexed keywords

3BETA (2 DIETHYLAMINOETHOXY)ANDROST 5 EN 17 ONE; CATALASE; CHOLESTEROL; DESMOSTEROL; FLUORESCENT DYE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; OXIDOSQUALENE CYCLASE INHIBITOR; SQUALENE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANISOTROPY; APOPTOSIS; ARTICLE; CATARACT; CATTLE; CONTROLLED STUDY; DRUG EFFECT; DRUG INDUCED DISEASE; EPITHELIUM CELL; EXPERIMENTAL ANIMAL; GROWTH INHIBITION; LENS EPITHELIUM; LIGHT SCATTERING; LIPOPHILICITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; X RAY DIFFRACTION;

ANDROSTENES; ANIMALS; APOPTOSIS; CATARACT; CATTLE; CELLS, CULTURED; ENZYME INHIBITORS; EPITHELIUM; INTRAMOLECULAR TRANSFERASES; LENS, CRYSTALLINE; MEMBRANE LIPIDS; MICE; PHASE TRANSITION; RATS; RATS, SPRAGUE-DAWLEY;

EID: 3042610068     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: 10.1194/jlr.M300469-JLR200     Document Type: Article

References (55)

1. Cenedella, R.J. 1996. Cholesterol and cataracts. Surv. Ophthalmol. 40: 320-337.
2. Hoffmann, G., K. M. Gibson, I. K. Brandt, P. I. Bader, R. S. Wappener, and L. Sweetman. 1986. Mevalonic aciduria-an inborn error of cholesterol and nonsterol isoprene biosynthesis. N. Engl. J. Med. 314: 1610-1614.
3. Derry, J. M., E. Gormally, G. D. Means, W. Zhao, A. Meindl, R. I. Kelley, Y. Boyd, and G. E. Herman. 1999. Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. Nat. Genet. 22: 286-290.
4. Tint, G. S., M. Irons, E. R. Elias, A. K. Batta, R. Frieden, T. S. Chen, and G. Salen. 1994. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N. Engl. J. Med. 330: 107-113.
5. FitzPatrick, D. R., J. W. Keeling, M.J. Evans, A. E. Kan, J. E. Bell, M. E. Porteous, K. Mills, R. M. Winter, and P. T. Clayton. 1998. Clinical phenotype of desmosterolosis. Am. J. Med. Genet. 75: 145-152.
6. von Sallmann, L. 1963. Triparanol-induced cataracts in rats. Trans. Am. Ophthalmol. Soc. 61: 49-60.
7. Cenedella, R.J., and G. G. Bierkamper. 1979. Mechanism of cataract production by 3-beta(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride, U18666A: an inhibitor of cholesterol biosynthesis. Exp. Eye Res. 28: 673-688.
8. Pyrah, I. T., A. Kalinowski, D. Jackson, W. Davies, S. Davis, A. Aldridge, and P. Greaves. 2001. Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse. Toxicol. Pathol. 29: 174-179.
9. Cenedella, R.J., J. R. Kuszak, K. J. Al-Ghoul, S. Qin, and P. S. Sexton. 2003. Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb:Thom rats. J. Lipid Res. 44: 198-211.
10. Schlienger, R. G., W. E. Haefeli, H. Jick, and C. R. Meier. 2001. Risk of cataract in patients treated with statins. Arch. Intern. Med. 161: 2021-2026.
11. Kantola, T., K. T. Kivisto, and P. J. Neuvonen. 1998. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin. Pharmacol. Ther. 64: 177-182.
12. Phillips, W. A., and J. Avigan. 1963. Inhibition of cholesterol biosynthesis in the rat by 3 beta-(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride. Proc. Soc. Exp. Biol. Med. 112: 233-236.
13. Mark, M., P. Muller, R. Maier, and B. Eisel. 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. Eisele, B., R. Budzinski, P. Muller, R. Maier, and M. Mark. 1997. Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo. J. Lipid Res. 38: 564-575.
15. Morand, O. H., J. D. Aebi, H. Dehmlow, Y. H. Ji, N. Gains, H. Lengsfeld, and J. Himber. 1997. Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J. Lipid Res. 38: 373-390.
16. Isaac, N. E., A. M. Walker, H.Jick, and M. Gorman. 1991. Exposure to phenothiazine drugs and risk of cataract. Arch. Ophthalmol. 109: 256-260.
17. Herbette, L., C. A. Napolitano, F. C. Messineo, and A. M. Katz. 1985. Interaction of amphiphilic molecules with biological membranes. A model for nonspecific and specific drug effects with membranes. Adv. Myocardiol. 5: 333-346.
18. Golden, G. A., P. E. Mason, R. T. Rubin, and R. P. Mason. 1998. Biophysical membrane interactions of steroid hormones: a potential complementary mechanism of steroid action. Clin. Neuropharmacol. 21: 181-189.
19. Fleschner, C. R., and R. J. Cenedella. 1991. Lipid composition of lens plasma membrane fractions enriched in fiber junctions. J. Lipid Res. 32: 45-53.
20. Rothblat, G. H., L. Y. Arbogast, L. Ouellette, and B. V. Howard. 1976. Preparation of delipidized serum protein for use in cell culture systems. In Vitro. 12: 554-557.
21. 3H]water for bovine lens epithelial cells in culture. J. Lipid Res. 26: 1455-1463.
22. 31P NMR quantification and monophasic solvent purification of human and bovine lens phospholipids. Lipids. 37: 1087-1092.
23. Chattopadhyay, A., and E. London. 1987. Parallax method for direct measurement of membrane penetration depth utilizing fluorescence quenching by spin-labeled phospholipids. Biochemistry. 26: 39-45.
24. Gidwani, A., D. Holowka, and B. Baird. 2001. Fluorescence anisotropy measurements of lipid order in plasma membranes and lipid rafts from RBL-2H3 mast cells. Biochemistry. 40: 12422-12429.
25. Bangham, A. D., M. M. Standish, and J. C. Watkins. 1965. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 13: 238-252.
26. Russell, P., W. G. Robison, Jr., and J. H. Kinoshita. 1981. A new method for rapid isolation of the intrinsic membrane proteins from lens. Exp. Eye Res. 32: 511-516.
27. Cenedella, R. J. 1982. Digitonide precipitable sterols: a reevaluation with special attention to lanosterol. Lipids. 17: 443-447.
28. Pollet, S., S. Ermidou, F. Le Saux, M. Monge, and N. Baumann. 1978. Microanalysis of brain lipids: multiple two-dimensional thinlayer chromatography. J. Lipid Res. 19: 916-921.
29. Borchman, D., R. J. Cenedella, and O. P. Lamba. 1996. Role of cholesterol in the structural order of lens membrane lipids. Exp. Eye Res. 62: 191-197.
30. Mason, R. P., W. J. Shoemaker, L. Shajenko, T. E. Chamers, and L. G. Herbette. 1992. Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol. Neurobiol. Aging. 13: 413-419.
31. Jacob, R. E., R. J. Cenedella, and R. P. Mason. 1999. Direct evidence for immiscible cholesterol domains in human ocular lens fiber cell plasma membranes. J. Biol. Chem. 274: 31613-31618.
32. Moody, M. F. 1963. X-ray diffraction pattern of nerve myelin: a method for determining the phases. Science. 142: 1173-1174.
33. Cenedella, R.J. 1985. Regional distribution of lipids and phospholipase A2 activity in normal and cataractous rat lens. Curr. Eye Res. 4: 113-120.
34. Takamura, Y., E. Kubo, S. Tsuzuki, and Y. Akagi. 2003. Apoptotic cell death in the lens epithelium of rat sugar cataracts. Exp. Eye Res. 77: 51-57.
35. Bhat, S. P. 2001. The ocular lens epithelium. Biosci. Rep. 21: 537-563.
36. Liscum, L., and J. R. Faust. 1989. The intracellular transport of low density lipoprotein derived cholesterol is inhibited in Chinese hamster ovary cells cultured with 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one. J. Biol. Chem. 264: 11796-11806.
37. Liscum, L., and K. W. Underwood. 1995. Intracellular cholesterol transport and compartmentation. J. Biol. Chem. 270: 15443-15446.
38. Feng, B., and I. Tabas. 2002. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity. J Biol Chem. 277: 43271-43280.
39. Cenedella, R. J. 1983. Source of cholesterol for the ocular lens, studied with U18666A: a cataract-producing inhibitor of lipid metabolism. Exp. Eye Res. 37: 33-43.
40. Kuszak, J. R., A. R. Khan, and R. J. Cenedella. 1988. An ultrastructural analysis of plasma membrane in the U18666A cataract. Invest. Ophthatmol Vis. Sci. 29: 261-267.
41. 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.
42. 3H]ifenprodil. Mol Pharmacol 54: 591-598.
43. Bae, S. H., and Y. K. Paik. 1997. Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol delta 24-reductase. Biochem. J. 326: 609-616.
44. Engelk, M., P. Bojarski, R. Bloss, and H. Diehl. 2001. Tamoxifen perturbs lipid bilayer order and permeability: comparison of DSC, fluorescence anisotropy, laurdan generalized polarization and carboxyfluorescein leakage studies. Biophys. Chem. 90: 157-173.
45. AstraZeneca. 2002. Novadex. In Physician's Desk Reference. Medical Economics Company, Montvale, NJ. Vol. 56. 678-684.
46. Gorin, M. B., R. Day, J. P. Constantino, B. Fisher, C. K. Redmond, L. Wickerham, J. E. Gomolin, R. G. Margolese, M. K. Mathen, D. M. Bowman, D. I. Kaufman, N. V. Dimitrov, L. J. Singerman, R. Bornstein, N. Wolmark, and D. Kaufmann. 1998. Long-term tamoxifen citrate use and potential ocular toxicity. Am. J. Ophthalmol. 125: 493-501.
47. Cenedella, R. J., C. P. Sarkar, and L. Towns. 1982. Studies on the mechanism of the epileptiform activity induced by U18666A. II. Concentration, half-life and distribution of radiolabeled U18666A in the brain. Epilepsia. 23: 257-268.
48. +-ATPase activity: relationship to steroid intercalation into the cell membrane. Life Sci. 65: 1247-1255.
49. Zeng, J., Z. Zhang, C. A. Paterson, S. Ferguson-Yankey, M. C. Yappert, and D. Borchman. 1999. Ca(2+)-ATPase activity and lens lipid composition in reconstituted systems. Exp. Eye Res. 69: 323-330.
50. Tang, D., D. Borchman, M. C. Yappert, G. F. Vrensen, and V. Rasi. 2003. Influence of age, diabetes, and cataract on calcium, lipid-calcium, and protein-calcium relationships in human lenses. Invest. Ophthalmol. Vis. Sci. 44: 2059-2066.
51. Li, W. C., J. R. Kuszak, K. Dunn, R. R. Wang, W. Ma, G. M. Wang, A. Spector, M. Leib, A. M. Cotliar, M. Weiss, J. Espy, G. Howard, R. L. Farris, J. Auran, A. Donn, A. Hofeldt, C. Mackay, J. Merriam, R. Mittl, and T. R. Smith. 1995. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals. J. Cell Biol. 130: 169-181.
52. Harocopos, G. J., K. M. Alvares, A. E. Kolker, and D. C. Beebe. 1998. Human age-related cataract and lens epithelial cell death. Invest. Ophthalmol. Vis. Sci. 39: 2696-2706.
53. Kellner-Weibel, G., Y.J. Geng, and G. H. Rothblat. 1999. Cytotoxic cholesterol deposition in macrophages mediated by cholesterol-enriched oxidized low density lipoproteins. Atherosclerosis. 146: 309-319.
54. Greenspan, P., H. Yu, F. Mao, and R. L. Gutman. 1997. Cholesterol deposition in macrophages: foam cell formation mediated by cholesterol-enriched oxidized low density lipoprotein. J. Lipid Res. 38: 101-109.
55. Smets, L. A., H. Van Rooij, and G. S. Salomons. 1999. Signalling steps in apoptosis by ether lipids. Apoptosis. 4: 419-427.