Identification of ACAT1 - and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: Individual ACAT uniqueness

Journal of Lipid Research

Volumn 45, Issue 2, 2004, Pages 378-386

  Lada, Aaron T ^a   Davis, Matthew ^a   Kent, Carol ^a   Chapman, James ^b   Tomoda, Hiroshi ^c   Omura, Satoshi ^c   Rudell, Lawrence L ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF SOUTH CAROLINA   (United States)

^c KITASATO INSTITUTE   (Japan)

Author keywords

Acyl CoA:cholesterol acyltransferase; Inhibitor; Pyripyropene A

Indexed keywords

CARBON 14; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; COMPLEMENTARY DNA; CP 113; ENZYME INHIBITOR; OLEIC ACID; PYRIPYROPENE A; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; ATHEROSCLEROSIS; CHOLESTEROL ESTERIFICATION; CHOLESTEROL METABOLISM; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; FLUORESCENCE; FLUORESCENCE MICROSCOPE; ISOTOPE LABELING; NONHUMAN; PRIORITY JOURNAL; THIN LAYER CHROMATOGRAPHY;

4-CHLORO-7-NITROBENZOFURAZAN; ANILINE COMPOUNDS; ANIMALS; CELL LINE, TUMOR; CHOLESTEROL; CRICETINAE; ENZYME INHIBITORS; INTESTINES; ISOENZYMES; LIVER; PYRIDINES; SESQUITERPENES; SPECTROMETRY, FLUORESCENCE; STEROL O-ACYLTRANSFERASE; SUBSTRATE SPECIFICITY; SULFIDES;

EID: 1242274634     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: 10.1194/jlr.D300037-JLR200     Document Type: Article

References (25)

1. Farese, R. V., Jr. 1998. Acyl CoA:cholesterol acyltransferase genes and knockout mice. Curr. Opin. Lipidol. 9: 119-123.
2. Anderson, R. A., C. Joyce, M. Davis, J. W. Reagan, M. Clark, G. S. Shelness, and L. L. Rudel. 1998. Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates. J. Biol. Chem. 273: 26747-26754.
3. Cases, S., S. J. Smith, Y. W. Zheng, H. M. Myers, S. R. Lear, E. Sande, S. Novak, C. Collins, C. B. Welch, A. J. Lusis, S. K. Erickson, and R. V. Farese. 1998. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc. Natl. Acad. Sci. USA. 95: 13018-13023.
4. Cases, S., S. Novak, Y. W. Zheng, H. M. Myers, S. R. Lear, E. Sande, C. B. Welch, A. J. Lusis, T. A. Spencer, B. R. Krause, S. K. Erickson, and R. V. Farese. 1998. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. J. Biol. Chem. 273: 26755-26764.
5. Oelkers, P. M., A. Behari, D. Cromley, J. T. Billheimer, and S. L. Sturley. 1998. Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. J. Biol. Chem. 273: 26765-26771.
6. Joyce, C. W., G. S. Shelness, M. A. Davis, R. G. Lee, K. Skinner, R. A. Anderson, and L. L. Rudel. 2000. ACAT1 and ACAT2 membrane topology segregates a serine residue essential for activity to opposite sides of the endoplasmic reticulum membrane. Mol. Biol. Cell. 11: 3675-3687.
7. Lee, R. G., M. C. Willingham, M. A. Davis, K. A. Skinner, and L. L. Rudel. 2000. Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates. J. Lipid Res. 41: 1991-2001.
8. Meiner, V. L., S. Cases, H. M. Myers, E. R. Sande, S. Bellosta, M. Schambelan, R. E. Pitas, J. McGuire, J. Herz, and R. V. Farese. 1996. Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals. Proc. Natl. Acad. Sci. USA. 93: 14041-14046.
9. Buhman, K. F., M. Accad, S. Novak, R. S. Choi, J. S. Wong, R. L. Hamilton, S. Turley, and R. V. Farese. 2000. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat. Med. 6: 1341-1347.
10. Accad, M., S. J. Smith, D. L. Newland, D. A. Sanan, L. E. King, Jr., M. F. Linton, S. Fazio, and R. V. Farese, Jr. 2000. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase I. J. Clin. Invest. 105: 711-719.
11. Yagyu, H., T. Kitamine, J. Osuga, R. Tozawa, Z. Chen, Y. Kaji, T. Oka, S. Perrey, Y. Tamura, K. Ohashi, H. Okazaki, N. Yahagi, F. Shionoir, Y. Iizuka, K. Harada, H. Shimano, H. Yamashita, T. Gotoda, N. Yamada, and S. Ishibashi. 2000. Absence of ACAT1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. J. Biol. Chem. 275: 21324-21330.
12. Fazio, S., A. S. Major, L. L. Swift, L. A. Gleaves, M. Accad, M. F. Linton, and R. V. Farese. 2001. Increased atherosclerosis in LDL-receptor-null mice lacking ACAT1 in macrophages. J. Clin. Invest. 107: 163-171.
13. Willner, E. L., B. Tow, K. F. Buhman, M. Wilson, D. A. Sanan, L. L. Rudel, and R. V. Farese. 2003. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc. Natl. Acad. Sci. USA. 100: 1262-1267.
14. Sparrow, C. P., S. Patel, J. Baffic, Y-S. Chao, M. Hernandez, M-H. Lam, J. Montenegro, S. D. Wright, and P. A. Detmers. 1999. A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro. J. Lipid Res. 40: 1747-1757.
15. van Meer, G., E. H. Stelzer, R. W. Wijnaendts-van-Resandt, and K. Simons. 1987. Sorting of sphingolipids in epithelial (Madin-Darby canine kidney) cells. J. Cell Biol. 105: 1623-1635.
16. Koval, M., and R. E. Pagano. 1990. Sorting of an internalized plasma membrane lipid between recycling and degradative pathways in normal and Niemann-Pick type A fibroblasts. J. Cell Biol. 111: 429-442.
17. Chattopadhyay, A., and E. London. 1988. Spectroscopic and ionization properties of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)4abeled lipids in model membranes. Biochim. Biophys. Acta. 938: 24-34.
18. Fery-Forgues, S., J. P. Fayet, and A. Lopez. 1993. Drastic changes in the fluorescence properties of NBD probes with the polarity of the medium: involvement of a TICT state? J. Photochem. Photobiol. 70: 229-243.
19. Mukherjee, S., A. Chattopadhyay, A. Samanta, and T. Soujanya. 1994. Dipole moment change of NBD group upon excitation using solvatochromic and quantum chemical approaches: implications in membrane research. J. Phys. Chem. 98: 2809-2812.
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. Omura, S., H. Tomoda, Y. Kim, and H. Nishida. 1993. Pyripyropenes, high potent inhibitors of acyl-CoA cholesterol acyltransferase produced by Aspergillus fumigatus. J. Antibiot. 46: 1168-1169.
22. Tomoda, H., Y. Kim, H. Nishida, R. Masuma, and S. Omura. 1994. Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. I. Production, isolation, and biological properties. J. Antibiot. 47: 148-153.
23. Chang, C. C., H. Y. Huh, K. M. Cadigan, and T. Y. Chang. 1993. Molecular cloning and functional expression of human acyl-coenzyme A:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells. J. Biol. Chem. 268: 20747-20755.
24. Ghosh, S., R. W. St. Clair, and L. L. Rudel. 2003. Mobilization of cytoplasmic cholesteryl ester droplets by over expression of human macrophage cholesterol ester hydrolase. J. Lipid Res. 44: 1833-1840.
25. Cho, K-H., S. An, W-S. Lee, Y-K. Paik, Y-K. Kim, and T-S. Jeong. 2003. Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Biochem. Biophys. Res. Comm. 309: 864-872.