HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Llirbat, B. Articles by Roux, C. Search for Related Content PubMed PubMed Citation Articles by Llirbat, B. Articles by Roux, C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 38, 22-34, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Normal and inhibited cholesterol synthesis in the cultured rat embryo

B Llirbat, C Wolf, F Chevy, D Citadelle, G Bereziat and C Roux
Laboratoire de Spectrometrie de masse, URA CNRS 1283, CHU Saint Antoine, Paris, France.

The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7-dehydrocholesterol reductase, the last enzymatic step in the cholesterol biosynthesis pathway. Development of the abnormal human fetus takes place in a normal environment as the heterozygous mother's cholesterolemia remains normal. An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766. In the animal model, embryonic development occurs in a disturbed environment characterized by hypocholesterolemia and accumulation of delta7-dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The purpose of the present study was to assess, in cultured rat embryos at early developmental stages, the relative contributions of exogenous and de novo synthesized cholesterol in the total embryonic cholesterol, according to the conditions of normal and altered de novo biosynthesis. Cultured rat embryos are able to synthesize cholesterol as shown by 13C-incorporation into cholesterol from 13C-labeled precursors added to the culture medium. De novo cholesterol biosynthesis is altered by addition to the culture medium of AY-9944 which inhibits the delta7-dehydrocholesterol reductase and the delta8- delta7-sterol isomerase as suggested by the emergence of characteristic aberrant sterols in the embryonic tissues. Cholesterol-rich serum used for embryo culture alters the pattern in a way that confirms that the rat embryos are able to import exogenous cholesterol which down- regulates de novo cholesterol biosynthesis. Exogenous cholesterol substitutes for the deficit in a manner efficient enough to prevent the embryonic abnormalities induced by AY-9944.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Yoshida and Y. Wada Transfer of maternal cholesterol to embryo and fetus in pregnant mice J. Lipid Res., October 1, 2005; 46(10): 2168 - 2174. [Abstract] [Full Text] [PDF]

				C. J. Thompson, S. M. Ross, and K. W. Gaido Di(n-Butyl) Phthalate Impairs Cholesterol Transport and Steroidogenesis in the Fetal Rat Testis through a Rapid and Reversible Mechanism Endocrinology, March 1, 2004; 145(3): 1227 - 1237. [Abstract] [Full Text] [PDF]

				P. A. Krakowiak, C. A. Wassif, L. Kratz, D. Cozma, M. Kovarova, G. Harris, A. Grinberg, Y. Yang, A. G.W. Hunter, M. Tsokos, et al. Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency Hum. Mol. Genet., July 1, 2003; 12(13): 1631 - 1641. [Abstract] [Full Text] [PDF]

				S. Ledoux, I. Runembert, K. Koumanov, J.B. Michel, G. Trugnan, and G. Friedlander Hypoxia Enhances Ecto-5'-Nucleotidase Activity and Cell Surface Expression in Endothelial Cells: Role of Membrane Lipids Circ. Res., May 2, 2003; 92(8): 848 - 855. [Abstract] [Full Text] [PDF]

				S. Ledoux, D. Laouari, M. Essig, I. Runembert, G. Trugnan, J.B. Michel, and G. Friedlander Lovastatin Enhances Ecto-5'-Nucleotidase Activity and Cell Surface Expression in Endothelial Cells: Implication of Rho-Family GTPases Circ. Res., March 8, 2002; 90(4): 420 - 427. [Abstract] [Full Text] [PDF]

				I. Runembert, G. Queffeulou, P. Federici, F. Vrtovsnik, E. Colucci-Guyon, C. Babinet, P. Briand, G. Trugnan, G. Friedlander, and F. Terzi Vimentin affects localization and activity of sodium-glucose cotransporter SGLT1 in membrane rafts J. Cell Sci., February 15, 2002; 115(4): 713 - 724. [Abstract] [Full Text] [PDF]

				B. Lindenthal, T. A. Aldaghlas, J. K. Kelleher, S. M. Henkel, R. Tolba, G. Haidl, and K. von Bergmann Neutral sterols of rat epididymis: high concentrations of dehydrocholesterols in rat caput epididymidis J. Lipid Res., July 1, 2001; 42(7): 1089 - 1095. [Abstract] [Full Text] [PDF]

				B. Ruan, W. K. Wilson, J. Pang, N. Gerst, F. D. Pinkerton, J. Tsai, R. I. Kelley, F. G. Whitby, D. M. Milewicz, J. Garbern, et al. Sterols in blood of normal and Smith-Lemli-Opitz subjects J. Lipid Res., May 1, 2001; 42(5): 799 - 812. [Abstract] [Full Text]

				B. Ruan, J. Tsai, W. K. Wilson, and G. J. Schroepfer , Jr. Aberrant pathways in the late stages of cholesterol biosynthesis in the rat: origin and metabolic fate of unsaturated sterols relevant to the Smith-Lemli-Opitz syndrome J. Lipid Res., November 1, 2000; 41(11): 1772 - 1782. [Abstract] [Full Text]

				E. Klapisz, J. Masliah, G. Béréziat, C. Wolf, and K. S. Koumanov Sphingolipids and cholesterol modulate membrane susceptibility to cytosolic phospholipase A2 J. Lipid Res., October 1, 2000; 41(10): 1680 - 1688. [Abstract] [Full Text]

				H. Yu, M.-H. Lee, L. Starck, E. R. Elias, M. Irons, G. Salen, S. B. Patel, and G. S. Tint Spectrum of {Delta}7-dehydrocholesterol reductase mutations in patients with the Smith-Lemli-Opitz (RSH) syndrome Hum. Mol. Genet., May 22, 2000; 9(9): 1385 - 1391. [Abstract] [Full Text] [PDF]

				C. Roux, C. Wolf, N. Mulliez, W. Gaoua, V. Cormier, F. Chevy, and D. Citadelle Role of cholesterol in embryonic development Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1270S - 1279. [Abstract] [Full Text] [PDF]

				W. Gaoua, C. Wolf, F. Chevy, F. Ilien, and C. Roux Cholesterol deficit but not accumulation of aberrant sterols is the major cause of the teratogenic activity in the Smith-Lemli-Opitz syndrome animal model J. Lipid Res., April 1, 2000; 41(4): 637 - 646. [Abstract] [Full Text]

				W. Gaoua, F. Chevy, C. Roux, and C. Wolf 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., March 1, 1999; 40(3): 456 - 463. [Abstract] [Full Text]

				S. K. Moestrup, R. Kozyraki, M. Kristiansen, J. H. Kaysen, H. H. Rasmussen, D. Brault, F. Pontillon, F. O. Goda, E. I. Christensen, T. G. Hammond, et al. The Intrinsic Factor-Vitamin B12 Receptor and Target of Teratogenic Antibodies Is a Megalin-binding Peripheral Membrane Protein with Homology to Developmental Proteins J. Biol. Chem., February 27, 1998; 273(9): 5235 - 5242. [Abstract] [Full Text] [PDF]

				F. F. Moebius, B. U. Fitzky, J. N. Lee, Y.-K. Paik, and H. Glossmann Molecular cloning and expression of the human Delta 7-sterol reductase PNAS, February 17, 1998; 95(4): 1899 - 1902. [Abstract] [Full Text] [PDF]

				J. Incardona, W Gaffield, R. Kapur, and H Roelink The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction Development, January 9, 1998; 125(18): 3553 - 3562. [Abstract] [PDF]

				S. Ledoux, D. Laouari, M. Essig, I. Runembert, G. Trugnan, J.B. Michel, and G. Friedlander Lovastatin Enhances Ecto-5'-Nucleotidase Activity and Cell Surface Expression in Endothelial Cells: Implication of Rho-Family GTPases Circ. Res., March 8, 2002; 90(4): 420 - 427. [Abstract] [Full Text] [PDF]