Biological activities of 7-dehydrocholesterol-derived oxysterols: Implications for Smith-Lemli-Opitz syndrome

Journal of Lipid Research

Volumn 51, Issue 11, 2010, Pages 3259-3269

  Korade, Zeljka ^b   Xu, Libin ^a   Shelton, Richard ^b   Porter, Ned A ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Free radical oxidation; Gene expression; Lipid peroxidation

Indexed keywords

7 DEHYDROCHOLESTEROL; OXYSTEROL;

ANIMAL CELL; ARTICLE; CELL FRACTIONATION; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; IMMUNOCYTOCHEMISTRY; LIPID ANALYSIS; MOUSE; NONHUMAN; OXIDATION; PATHOPHYSIOLOGY; PEROXIDATION; PRIORITY JOURNAL; SMITH LEMLI OPITZ SYNDROME;

ANIMALS; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DEHYDROCHOLESTEROLS; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION PROFILING; MICE; NEURONS; OXIDATION-REDUCTION; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PEROXIDES; SMITH-LEMLI-OPITZ SYNDROME; TIME FACTORS;

EID: 78149314221     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M009365     Document Type: Article

References (75)

1. Porter, N. A. 1986. Mechanisms for the autoxidation of polyunsaturated lipids. Acc. Chem. Res. 19: 262-270.
2. Porter, N. A., S. E. Caldwell, and K. A. Mills. 1995. Mechanisms of free radical oxidation of unsaturated lipids. Lipids. 30: 277-290.
3. Yin, H., and N. A. Porter. 2005. New insights regarding the autoxidation of polyunsaturated fatty acids. Antioxid. Redox Signal. 7: 170-184.
4. Porter, N. A., M. O. Funk, D. W. Gilmore, R. Isaac, and J. Nixon. 1976. The formation of cyclic peroxides from unsaturated hydroperoxides: models for prostaglandin biosynthesis. J. Am. Chem. Soc. 98: 6000-6005.
5. Porter, N. A., B. A. Weber, H. Weenen, and J. A. Khan. 1980. Autoxidation of polyunsaturated lipids. Factors controlling the stereochemistry of product hydroperoxides. J. Am. Chem. Soc. 102: 5597-5601.
6. Pratt, D. A., J. H. Mills, and N. A. Porter. 2003. Theoretical calculations of carbon-oxygen bond dissociation enthalpies of peroxyl radicals formed in the autoxidation of lipids. J. Am. Chem. Soc. 125: 5801-5810.
7. Xu, L., T. A. Davis, and N. A. Porter. 2009. Rate constants for peroxidation of polyunsaturated fatty acids and sterols in solution and in liposomes. J. Am. Chem. Soc. 131: 13037-13044.
8. Korcek, S., J. H. B. Chenier, J. A. Howard, and K. U. Ingold. 1972. Absolute rate constants for hydrocarbon autoxidation. 21. Activation-energies for propagation and correlation of propagation rate constants with carbon-hydrogen bond strengths. Can. J. Chem. 50: 2285-2297.
9. Smith, D. W., L. Lemli, and J. M. Opitz. 1964. A newly recognized syndrome of multiple congenital anomalies. J. Pediatr. 64: 210-217.
10. 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.
11. Tint, G. S., M. Seller, R. Hughes-Benzie, A. K. Batta, S. Shefer, D. Genest, M. Irons, E. Elias, and G. Salen. 1995. Markedly increased tissue concentrations of 7-dehydrocholesterol combined with low levels of cholesterol are characteristic of the Smith-Lemli-Opitz syndrome. J. Lipid Res. 36: 89-95.
12. Jira, P. E., R. J. Wanders, J. A. Smeitink, J. De Jong, R. A. Wevers, W. Oostheim, J. H. Tuerlings, R. C. Hennekam, R. C. Sengers, and H. R. Waterham. 2001. Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith-Lemli-Opitz syndrome. Ann. Hum. Genet. 65: 229-236.
13. Krakowiak, P. A., N. A. Nwokoro, C. A. Wassif, K. P. Battaile, M. J. Nowaczyk, W. E. Connor, C. Maslen, R. D. Steiner, and F. D. Porter. 2000. Mutation analysis and description of sixteen RSH/Smith- Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping. Am. J. Med. Genet. 94: 214-227.
14. Salen, G., S. Shefer, A. K. Batta, G. S. Tint, G. Xu, A. Honda, M. Irons, and E. R. Elias. 1996. Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome. J. Lipid Res. 37: 1169-1180.
15. Witsch-Baumgartner, M., J. Loffler, and G. Utermann. 2001. Mutations in the human DHCR7 gene. Hum. Mutat. 17: 172-182.
16. Honda, A., G. S. Tint, G. Salen, A. K. Batta, T. S. Chen, and S. Shefer. 1995. Defective conversion of 7-dehydrocholesterol to cholesterol in cultured skin fibroblasts from Smith-Lemli-Opitz syndrome homozygotes. J. Lipid Res. 36: 1595-1601.
17. Kelley, R. I., and R. C. Hennekam. 2000. The Smith-Lemli-Opitz syndrome. J. Med. Genet. 37: 321-335.
18. Porter, F. D. 2003. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr. Opin. Pediatr. 15: 607-613.
19. Sikora, D. M., K. Pettit-Kekel, J. Penfield, L. S. Merkens, and R. D. Steiner. 2006. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am. J. Med. Genet. A. 140: 1511-1518.
20. Bukelis, I., F. D. Porter, A. W. Zimmerman, and E. Tierney. 2007. Smith-Lemli-Opitz syndrome and autism spectrum disorder. Am. J. Psychiatry. 164: 1655-1661.
21. Gaoua, W., F. Chevy, C. Roux, and C. Wolf. 1999. Oxidized derivatives of 7-dehydrocholesterol induce growth retardation in cultured rat embryos: a model for antenatal growth retardation in the Smith- Lemli-Opitz syndrome. J. Lipid Res. 40: 456-463. (Pubitemid 29116149)
22. Richards, M. J., B. A. Nagel, and S. J. Fliesler. 2006. Lipid hydroperoxide formation in the retina: correlation with retinal degeneration and light damage in a rat model of Smith-Lemli-Opitz syndrome. Exp. Eye Res. 82: 538-541.
23. Schroepfer, G. J., Jr. 2000. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol. Rev. 80: 361-554.
24. Valencia, A., A. Rajadurai, A. B. Carle, and I. E. Kochevar. 2006. 7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: roles of NADPH oxidase, mitochondria, and lipid rafts. Free Radic. Biol. Med. 41: 1704-1718.
25. Lee, J. W., J. Sanchez, R. Riddick, J-D. Huang, S. J. Fliesler, and I. R. Rodriguez. 2009. Potentiation of visible light-induced photodamage in cultured RPE cells by treatment with AY9944, a 7-dehydrocholesterol reductase inhibitor. (Abstract #1843 in Annual Meeting Association for Research in Vision and Ophthalmology, Ft. Lauderdale, FL).
26. Tint, G. S., A. K. Batta, G. Xu, S. Shefer, A. Honda, M. Irons, E. R. Elias, and G. Salen. 1997. The Smith-Lemli-Opitz syndrome: a potentially fatal birth defect caused by a block in the last enzymatic step in cholesterol biosynthesis. Subcell. Biochem. 28: 117-144.
27. Dietschy, J. M., and S. D. Turley. 2001. Cholesterol metabolism in the brain. Curr. Opin. Lipidol. 12: 105-112.
28. Haas, D., S. F. Garbade, C. Vohwinkel, N. Muschol, F. K. Trefz, J. M. Penzien, J. Zschocke, G. F. Hoffmann, and P. Burgard. 2007. Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). J. Inherit. Metab. Dis. 30: 375-387.
29. Sikora, D. M., M. Ruggiero, K. Petit-Kekel, L. S. Merkens, W. E. Connor, and R. D. Steiner. 2004. Cholesterol supplementation does not improve developmental progress in Smith-Lemli-Opitz syndrome. J. Pediatr. 144: 783-791.
30. Starck, L., A. Lovgren-Sandblom, and I. Bjorkhem. 2002. Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome. J. Intern. Med. 252: 314-321.
31. Tierney, E., S. K. Conley, H. Goodwin, and F. D. Porter. 2010. Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz syndrome. Am. J. Med. Genet. A. 152A: 91-95.
32. Xu, L., Z. Korade, and N. A. Porter. 2010. Oxysterols from free radical chain oxidation of 7-dehydrocholesterol: product and mechanistic studies. J. Am. Chem. Soc. 132: 2222-2232.
33. Brown, A. J., and W. Jessup. 2009. Oxysterols: Sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol. Aspects Med. 30: 111-122.
34. Javitt, N. B. 2008. Oxysterols: novel biologic roles for the 21st century. Steroids. 73: 149-157.
35. Lemaire-Ewing, S., C. Prunet, T. Montange, A. Vejux, A. Berthier, G. Bessede, L. Corcos, P. Gambert, D. Neel, and G. Lizard. 2005. Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols. Cell Biol. Toxicol. 21: 97-114.
36. Smith, W. L., and R. C. Murphy. 2008. Oxidized lipids formed non-enzymatically by reactive oxygen species. J. Biol. Chem. 283: 15513-15514.
37. Murphy, R. C., and K. M. Johnson. 2008. Cholesterol, reactive oxygen species, and the formation of biologically active mediators. J. Biol. Chem. 283: 15521-15525.
38. Vejux, A., and G. Lizard. 2009. Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/ or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol. Aspects Med. 30: 153-170.
39. Pearson, A., Y. Chen, G. Han, S. Hsu, and T. Ray. 1985. A new method for the oxidation of alkenes to enones: an efficient synthesis of delta-5-7-oxo steroids. J. Chem. Soc. Perkins Trans. I. 267-273.
40. Korade, Z., A. K. Kenworthy, and K. Mirnics. 2009. Molecular consequences of altered neuronal cholesterol biosynthesis. J. Neurosci. Res. 87: 866-875.
41. Korade, Z., Z. Mi, C. Portugal, and N. F. Schor. 2007. Expression and p75 neurotrophin receptor dependence of cholesterol synthetic enzymes in adult mouse brain. Neurobiol. Aging. 28: 1522-1531.
42. Albro, P. W., P. Bilski, J. T. Corbett, J. L. Schroeder, and C. F. Chignell. 1997. Photochemical reactions and phototoxicity of sterols: novel self-perpetuating mechanisms for lipid photooxidation. Photochem. Photobiol. 66: 316-325.
43. Albro, P. W., J. T. Corbett, and J. L. Schroeder. 1994. Doubly allylic hydroperoxide formed in the reaction between sterol 5,7-dienes and singlet oxygen. Photochem. Photobiol. 60: 310-315.
44. Bindoli, A., J. M. Fukuto, and H. J. Forman. 2008. Thiol chemistry in peroxidase catalysis and redox signaling. Antioxid. Redox Signal. 10: 1549-1564.
45. Comhair, S. A., and S. C. Erzurum. 2005. The regulation and role of extracellular glutathione peroxidase. Antioxid. Redox Signal. 7: 72-79.
46. Ursini, F., M. Maiorino, and C. Gregolin. 1985. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta. 839: 62-70.
47. Berthier, A., S. Lemaire-Ewing, C. Prunet, S. Monier, A. Athias, G. Bessede, J. P. Pais de Barros, A. Laubriet, P. Gambert, G. Lizard, et al. 2004. Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis. Cell Death Differ. 11: 897-905.
48. Nelson, T. J., and D. L. Alkon. 2005. Oxidation of cholesterol by amyloid precursor protein and beta-amyloid peptide. J. Biol. Chem. 280: 7377-7387.
49. Gerdes, J., H. Lemke, H. Baisch, H. H. Wacker, U. Schwab, and H. Stein. 1984. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J. Immunol. 133: 1710-1715. (Pubitemid 14035254)
50. Theodorou, E., G. Dalembert, C. Heffelfinger, E. White, S. Weissman, L. Corcoran, and M. Snyder. 2009. A high throughput embryonic stem cell screen identifies Oct-2 as a bifunctional regulator of neuronal differentiation. Genes Dev. 23: 575-588.
51. Chao, M. V. 1994. The p75 neurotrophin receptor. J. Neurobiol. 25: 1373-1385.
52. Comporti, M., C. Signorini, B. Arezzini, D. Vecchio, B. Monaco, and C. Gardi. 2008. F2-isoprostanes are not just markers of oxidative stress. Free Radic. Biol. Med. 44: 247-256.
53. van Reyk, D. M., A. J. Brown, L. M. Hult'en, R. T. Dean, and W. Jessup. 2006. Oxysterols in biological systems: sources, metabolism and pathophysiological relevance. Redox Rep. 11: 255-262.
54. Wang, L., G. U. Schuster, K. Hultenby, Q. Zhang, S. Andersson, and J. A. Gustafsson. 2002. Liver X receptors in the central nervous system: from lipid homeostasis to neuronal degeneration. Proc. Natl. Acad. Sci. USA. 99: 13878-13883.
55. Edwards, P. A., M. A. Kennedy, and P. A. Mak. 2002. LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis. Vascul. Pharmacol. 38: 249-256.
56. Zhao, C., and K. Dahlman-Wright. 2010. Liver X receptor in cholesterol metabolism. J. Endocrinol. 204: 233-240.
57. Janowski, B. A., M. J. Grogan, S. A. Jones, G. B. Wisely, S. A. Kliewer, E. J. Corey, and D. J. Mangelsdorf. 1999. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA. 96: 266-271.
58. Janowski, B. A., P. J. Willy, T. R. Devi, J. R. Falck, and D. J. Mangelsdorf. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 383: 728-731.
59. Lehmann, J. M., S. A. Kliewer, L. B. Moore, T. A. Smith-Oliver, B. B. Oliver, J. L. Su, S. S. Sundseth, D. A. Winegar, D. E. Blanchard, T. A. Spencer, et al. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. 272: 3137-3140.
60. Spencer, T. A., D. Li, J. S. Russel, J. L. Collins, R. K. Bledsoe, T. G. Consler, L. B. Moore, C. M. Galardi, D. D. McKee, J. T. Moore, et al. 2001. Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha. J. Med. Chem. 44: 886-897.
61. Handschin, C., and U. A. Meyer. 2005. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch. Biochem. Biophys. 433: 387-396.
62. Im, Y. J., S. Raychaudhuri, W. A. Prinz, and J. H. Hurley. 2005. Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature. 437: 154-158.
63. Fliesler, S. J. 2010. Retinal degeneration in a rat model of smith-lemli-opitz syndrome: thinking beyond cholesterol deficiency. Adv. Exp. Med. Biol. 664: 481-489.
64. Herman, G. E. 2003. Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Hum. Mol. Genet. 12: R75-R88.
65. Engelking, L. J., B. M. Evers, J. A. Richardson, J. L. Goldstein, M. S. Brown, and G. Liang. 2006. Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin. J. Clin. Invest. 116: 2356-2365.
66. Porter, F. D. 2006. Cholesterol precursors and facial clefting. J. Clin. Invest. 116: 2322-2325.
67. Evers, B. M., M. S. Farooqi, J. M. Shelton, J. A. Richardson, J. L. Goldstein, M. S. Brown, and G. Liang. 2010. Hair growth defects in Insig-deficient mice caused by cholesterol precursor accumulation and reversed by simvastatin. J. Invest. Dermatol. 130: 1237-1248.
68. Engelking, L. J., G. Liang, R. E. Hammer, K. Takaishi, H. Kuriyama, B. M. Evers, W. P. Li, J. D. Horton, J. L. Goldstein, and M. S. Brown. 2005. Schoenheimer effect explained-feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J. Clin. Invest. 115: 2489-2498.
69. Pulfer, M. K., and R. C. Murphy. 2004. Formation of biologically active oxysterols during ozonolysis of cholesterol present in lung surfactant. J. Biol. Chem. 279: 26331-26338.
70. Vaughan, D. K., N. S. Peachey, M. J. Richards, B. Buchan, and S. J. Fliesler. 2006. Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Exp. Eye Res. 82: 496-504.
71. Wassif, C. A., P. Zhu, L. Kratz, P. A. Krakowiak, K. P. Battaile, F. F. Weight, A. Grinberg, R. D. Steiner, N. A. Nwokoro, R. I. Kelley, et al. 2001. Biochemical, phenotypic and neurophysiological characterization of a genetic mouse model of RSH/Smith-Lemli-Opitz syndrome. Hum. Mol. Genet. 10: 555-564.
72. Fitzky, B. U. 2001. 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome. J Clin Invest 108: 905-915.
73. Fliesler, S. J., N. S. Peachey, M. J. Richards, B. A. Nagel, and D. K. Vaughan. 2004. Retinal degeneration in a rodent model of Smith- Lemli-Opitz syndrome: electrophysiologic, biochemical, and morphologic features. Arch. Ophthalmol. 122: 1190-1200.
74. Wang, Y., K. M. Sousa, K. Bodin, S. Theofilopoulos, P. Sacchetti, M. Hornshaw, G. Woffendin, K. Karu, J. Sjovall, E. Arenas, et al. 2009. Targeted lipidomic analysis of oxysterols in the embryonic central nervous system. Mol. Biosyst. 5: 529-541.
75. Waage-Baudet, H., J. M. Lauder, D. B. Dehart, K. Kluckman, S. Hiller, G. S. Tint, and K. K. Sulik. 2003. Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism. Int. J. Dev. Neurosci. 21: 451-459.