Early steps in reverse cholesterol transport: Cholesteryl ester hydrolase and other hydrolases

Current Opinion in Endocrinology, Diabetes and Obesity

Volumn 19, Issue 2, 2012, Pages 136-141

  Ghosh, Shobha ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

atherosclerosis; functional redundancy; gene ablation deficiency; macrophage cholesteryl ester hydrolysis; responsive backup circuits

Indexed keywords

ARYLACETAMIDE DEACETYLASE LIKE 1; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ESTERASE; HORMONE SENSITIVE LIPASE; HYDROLASE; LOW DENSITY LIPOPROTEIN RECEPTOR; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; CHOLESTEROL TRANSPORT; GENE OVEREXPRESSION; GLUCOSE TOLERANCE; HUMAN; INFLAMMATION; INSULIN SENSITIVITY; INTRACELLULAR SPACE; LIPID HYDROLYSIS; MACROPHAGE; NONHUMAN; REVIEW;

ANIMALS; ATHEROSCLEROSIS; BIOLOGICAL TRANSPORT; CHOLESTEROL ESTERS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; HYDROLASES; MICE; MICE, KNOCKOUT; STEROL ESTERASE;

EID: 84858279956     PISSN: 1752296X     EISSN: 17522978     Source Type: Journal    
DOI: 10.1097/MED.0b013e3283507836     Document Type: Review

References (43)

1. van der Velde AE. Reverse cholesterol transport: from classical view to new insights. World J Gastroenterol 2010; 16:5908-5915. This review summarizes the current knowledge of the process and molecular components of RCT along with a brief introduction to the emerging view of alternate mechanism of cholesterol elimination or TICE.
2. Ghosh S, Zhao B, Bie J, Song J. Macrophage cholesteryl ester mobilization and atherosclerosis. Vascul Pharmacol 2010; 52:1-10. This review systematically discusses the controversies related to macrophage CEHs and provides a direct comparison of the enzymes characterized thus far. The issues related to the physical state of the substrate used for the measurement of enzyme activity in vitro are also discussed to provide the reason for discordant results.
3. Goldberg DI, Khoo JC. Stimulation of neutral cholesteryl ester hydrolase by cAMP in P388D1 macrophages. Biochim Biophys Acta 1990; 1042:132-137. (Pubitemid 20021625)
4. Small CA, Goodacre JA, Yeaman SJ. Hormone sensitive lipase is responsible for the neutral cholesteryl ester hydrolase activity in macrophages. FEBS Lett 1989; 247:205-208. (Pubitemid 19129248)
5. Khoo JC, Reue K, Steinberg D, Schotz MC. Expression of hormone-sensitive lipase mRNA in macrophages. J Lipid Res 1993; 34:1969-1974. (Pubitemid 23324971)
6. Johnson WJ, Jang SY, Bernard DW. Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line. Comp Biochem Physiol B Biochem Mol Biol 2000; 126:543-552. (Pubitemid 30628383)
7. Li F, Hui DY. Modified low density lipoprotein enhances the secretion of bile salt-stimulated cholesterol esterase by human monocyte-macrophages. Species- specific difference in macrophage cholesteryl ester hydrolase. J Biol Chem 1997; 272:28666-28671. (Pubitemid 27517822)
8. Reue K, Cohen RD, Schotz MC. Evidence for hormone-sensitive lipase mRNA expression in human monocyte/macrophages. Arterioscler Thromb Vasc Biol 1997; 17:3428-3432. (Pubitemid 28028552)
9. Osuga J, Ishibashi S, Oka T, et al. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A 2000; 97:787-792. (Pubitemid 30070388)
10. Contreras JA. Hormone sensitive lipase is not required for cholesteryl ester hydrolysis in macrophages. Biochem Biophys Res Comm 2002; 292:900-903. (Pubitemid 34687289)
11. Buchebner M, Pfeifer T, Rathke N, et al. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. J Lipid Res 2010; 51:2896-2908. These studies compare the hydrolytic activity toward various substrates and highlight the discordance between in-vitro assays and in-vivo effects.
12. Sekiya M, Osuga J, Yahagi N, et al. Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis. J Lipid Res 2008; 49:1829-1838.
13. Fernandez C, Lindholm M, Krogh M, et al. Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice. Am J Physiol Endocrinol Metab 2008; 295:E820-E831.
14. Ghosh S, Grogan WM. Rapid three-step purification of a hepatic neutral cholesteryl ester hydrolase which is not the pancreatic enzyme. Lipids 1991; 10:793-798.
15. Ghosh S, Mallonee DH, Hylemon PB, Grogan WM. Molecular cloning and expression of rat hepatic neutral cholesteryl ester hydrolase. Biochim Biophys Acta 1995; 1259:305-312. (Pubitemid 26014984)
16. Ghosh S. Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing and expression of full-length cDNA. Physiol Genomics 2000; 2:1-8.
17. Zhao B, Fisher BJ, St Clair RW, et al. Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to lipid droplets upon lipid loading. J Lipid Res 2005; 46:2114-2121. (Pubitemid 41377463)
18. Ghosh S, St Clair RW, Rudel LL. Mobilization of cytoplasmic CE droplets by over-expression of human macrophage cholesteryl ester hydrolase. J Lipid Res 2003; 44:1833-1840. (Pubitemid 37356655)
19. Zhao B, Song J, St Clair RW, Ghosh S. Stable over-expression of human macrophage cholesteryl ester hydrolase (CEH) results in enhanced free cholesterol efflux from human THP1-macrophages. Am J Physiol Cell Physiol 2007; 292:C405-C412. (Pubitemid 46115148)
20. Crow JA, Middleton BL, Borazjani A, et al. Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochim Biophys Acta 2008; 1781:643-654.
21. Zhao B, Song J, Chow WN, et al. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr-/- mice. J Clin Invest 2007; 117:2983-2992. (Pubitemid 47529628)
22. Bie J, Zhao B, Song J, Ghosh S. Improved insulin sensitivity in high fat- and high cholesterol-fed Ldlr-/- mice with macrophage-specific transgenic expression of cholesteryl ester hydrolase: role of macrophage inflammation and infiltration into adipose tissue. J Biol Chem 2010; 285:13630-13637. This study provides strong evidence for the role of macrophage cholesterol homeostasis in regulating systemic as well as adipose tissue inflammation. Targeted decrease in macrophage cholesterol content is established as a possible common mechanism to simultaneously attenuate inflammation-linked diseases such as diabetes and atherosclerosis.
23. Bie J, Zhao B, Ghosh S. Atherosclerotic lesion progression is attenuated by reconstitution with bone marrow from macrophage-specific cholesteryl ester hydrolase transgenic mice. Am J Physiol Regul Integr Comp Physiol 2011; 301:R967-R974. Genetic manipulations have succeeded in attenuating atherosclerosis, but little information is available about strategies to prevent or reduce lesion progression. This study shows for the first time that if removal of cholesteryl ester from macrophages is enhanced even after the lesion development has started, this strategy will attenuate lesion progression underscoring the importance of developing ways to increase macrophage cholesteryl ester hydrolysis as a potential therapy for preventing atherosclerotic plaque progression.
24. Zhao B, Natarajan R, Ghosh S. Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis. Physiol Genomics 2005; 23:304-310. (Pubitemid 44437966)
25. Zhao B, Song J, Ghosh S. Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol elimination and in vivo reverse cholesterol transport. J Lipid Res 2008; 49:2212-2217.
26. Dolinsky VW, Sipione S, Lehner R, Vance DE. The cloning and expression of a murine triacylglycerol hydrolase cDNA and the structure of its corresponding gene. Biochim Biophys Acta 2001; 1532:162-172. (Pubitemid 32706436)
27. Quiroga AD, Lehner R. Role of endoplasmic reticulum neutral lipid hydrolases. Trends Endocrinol Met 2011; 22:218-225. Detailed review of enzymes involved in neutral lipid hydrolysis with emphasis on controversies and limitations of the published studies.
28. Wei E, Ben Ali Y, Lyon J, et al. Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure. Cell Metab 2010; 11:183-193. Another study that shows incomplete loss of hydrolytic activity by single gene ablation and provides evidence for possible redundancy.
29. Okazaki H, Igarashi M, Nishi M, et al. Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages. J Biol Chem 2008; 283:33357-33364.
30. Sekiya M, Osuga J, Nagashima S, et al. Ablation of neutral cholesterol ester hydrolase 1 accelerates atherosclerosis. Cell Metab 2009; 10:219-228.
31. Igarashi M, Osuga J, Uozaki H, et al. The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages. Circ Res 2010; 107:1387-1395. Data from this study provide evidence for incomplete loss of intracellular cholesteryl ester hydrolytic activity by gene knockdown studies and form the strong basis for the concept of redundancy and compensation.
32. Nomura DK, Durkin KA, Chiang KP, et al. Serine hydrolase KIAA1363: toxicological and structural features with emphasis on organophosphate interactions. Chem Res Toxicol 2006; 19:1142-1150. (Pubitemid 44454030)
33. Ouimet M, Franklin V, Mak E, et al. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab 2011; 13:655-667. This study challenges the existing paradigm of cytoplasmic hydrolysis of macrophage cholesteryl ester without the involvement of the acidic compartment. Evidence is presented for a novel mechanism in which cholesteryl ester-containing lipid droplets are delivered to the lysosomes by autophage and lysosomal acid lipase is involved in cholesteryl ester hydrolysis.
34. Brufau G, Groen AK, Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion. Arterioscler Thromb Vasc Biol 2011; 31:1726-1733. A timely comparison of RCT and TICE.
35. Temel RE, Sawyer JK, Yu L, et al. Biliary sterol secretion is not required for macrophage reverse cholesterol transport. Cell Metab 2010; 12:96-102. Strong data are presented to demonstrate nonbiliary route of cholesterol elimination. A new paradigm is presented in which contribution of the classical RCT pathway to fecal sterol excretion is marginal compared to TICE.
36. Temel RE, Brown JM. A new framework for reverse cholesterol transport: nonbiliary contributions to reverse cholesterol transport. World J Gastroenterol 2010; 16:5946-5952. Review of the newly identified mechanism of TICE as an important player in elimination of cholesterol from the body. The current understanding of the molecular components involved in TICE is reviewed.
37. Camarota LM, Woollett LA, Howles PN. Reverse cholesterol transport is elevated in carboxyl ester lipase-knockout mice. FASEB J 2011; 25:1370-1377. First study to link loss of a CEH and increase in cholesterol elimination from the body providing evidence for CEL involvement in intestinal cholesteryl ester hydrolysis and possibly TICE.
38. Kodvawala A, Ghering AB, Davidson WS, Hui DY. Carboxyl ester lipase expression in macrophages increases cholesteryl ester accumulation and promotes atherosclerosis. J Biol Chem 2005; 280:38592-38598. (Pubitemid 43853760)
39. Nowak MA, Boerlijst MC, Cooke J, Smith JM. Evolution of genetic redundancy. Nature 1997; 388:167-171.
40. Kafri R, Springer M, Pilpel Y. Genetic redundancy: new tricks for old genes. Cell 2009; 136:389-392.
41. Kafri R, Levy M, Pilpel Y. The regulatory utilization of genetic redundancy through responsive backup circuits. Proc Natl Acad Sci U S A 2006; 103:11653-11658. (Pubitemid 44182506)
42. Porter JD, Rafael JA, Ragusa RJ, et al. The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin. Cell Sci 1998; 111:1801-1811. (Pubitemid 28370525)
43. Deconinck AE, Rafael JA, Skinner JA, et al. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 1997; 90:717-727. (Pubitemid 27357963)