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

J. Biol. Chem., Vol. 277, Issue 37, 34036-34041, September 13, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/37/34036    most recent M201122200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Meir, K. Articles by Leitersdorf, E. Search for Related Content PubMed PubMed Citation Articles by Meir, K. Articles by Leitersdorf, E. Social Bookmarking                      What's this?

Human Sterol 27-Hydroxylase (CYP27) Overexpressor Transgenic Mouse Model
EVIDENCE AGAINST 27-HYDROXYCHOLESTEROL AS A CRITICAL REGULATOR OF CHOLESTEROL HOMEOSTASIS^*

Karen Meir^§, Daniel Kitsberg^§, Irit Alkalay^§, Fanny Szafer^§, Haim Rosen^¶, Shoshanna Shpitzen^§, Liat Ben Avi^§, Bart Staels, Catherine Fievet, Vardiella Meiner^**, Ingemar Björkhem, and Eran Leitersdorf^§§§¶¶

From the Departments of  Pathology, ^** Human Genetics, and ^§§ Medicine B and the ^§ Center for Research, Prevention, and Treatment of Atherosclerosis, Hadassah University Hospital, 91120 Jerusalem, Israel, the ^¶ Department of Molecular Virology, Faculty of Medicine, Hebrew University, 91120 Jerusalem, Israel, the  Department of Atherosclerosis, Institut Pasteur de Lille, 59000 Lille, France, and the  Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Huddinge, Sweden

CYP27-overexpressed transgenic mice were generated with the use of a human full-length CYP27 coding region cloned into a ubiquitous expression vector. Positive transgenic mice were identified by tail DNA genotyping and high fecal 27-hydroxycholesterol content. The levels of 27-hydroxycholesterol were found to be 3-5 times higher in the circulation and the tissues of the overexpressed mice when compared with littermate controls. There were no gross morphological differences between the overexpressed mice and their controls. Total cholesterol and triglyceride levels were not affected by overexpression of CYP27. Serum lathosterol was also normal, suggesting a normal rate of cholesterol synthesis. Serum levels of 7-hydroxycholesterol were unaffected, suggesting a normal rate of bile acid formation in the pathway involving cholesterol 7-hydroxylase. Biliary bile acid composition was slightly affected by CYP27 overexpression in female but not in male mice. Fecal levels of neutral steroids were slightly but significantly increased in overexpressor female mice but not in male mice. Levels of 24-hydroxycholesterol in the circulation were significantly reduced in the overexpressed mice, probably as a consequence of a recently described catabolic pathway involving CYP27. Combined with the results of our previous work on mice with a disruption of the CYP27 gene, the present results suggest that the levels of 27-hydroxycholesterol are not of critical importance for cholesterol homeostasis in mice.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. Bjorkhem Are side-chain oxidized oxysterols regulators also in vivo? J. Lipid Res., April 1, 2009; 50(Supplement): S213 - S218. [Abstract] [Full Text] [PDF]

				N. Mukhamedova, G. Escher, W. D'Souza, U. Tchoua, A. Grant, Z. Krozowski, M. Bukrinsky, and D. Sviridov Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo J. Lipid Res., November 1, 2008; 49(11): 2312 - 2322. [Abstract] [Full Text] [PDF]

				X. Li, W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren Biosynthesis of the regulatory oxysterol, 5-cholesten-3{beta},25-diol 3-sulfate, in hepatocytes J. Lipid Res., December 1, 2007; 48(12): 2587 - 2596. [Abstract] [Full Text] [PDF]

				S.-P. Tam, L. Mok, G. Chimini, M. Vasa, and R. G. Deeley ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells Am J Physiol Cell Physiol, September 1, 2006; 291(3): C490 - C502. [Abstract] [Full Text] [PDF]

				I. A. Pikuleva CHOLESTEROL-METABOLIZING CYTOCHROMES P450 Drug Metab. Dispos., April 1, 2006; 34(4): 513 - 520. [Abstract] [Full Text] [PDF]

				J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]

				S. Dubrac, S. R. Lear, M. Ananthanarayanan, N. Balasubramaniyan, J. Bollineni, S. Shefer, H. Hyogo, D. E. Cohen, P. J. Blanche, R. M. Krauss, et al. Role of CYP27A in cholesterol and bile acid metabolism J. Lipid Res., January 1, 2005; 46(1): 76 - 85. [Abstract] [Full Text] [PDF]

				J. F. Oram HDL Apolipoproteins and ABCA1: Partners in the Removal of Excess Cellular Cholesterol Arterioscler. Thromb. Vasc. Biol., May 1, 2003; 23(5): 720 - 727. [Abstract] [Full Text] [PDF]

				M. Fuchs Bile Acid Regulation of Hepatic Physiology: III. Regulation of bile acid synthesis: past progress and future challenges Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G551 - G557. [Abstract] [Full Text] [PDF]

				G. Escher, Z. Krozowski, K. D. Croft, and D. Sviridov Expression of Sterol 27-Hydroxylase (CYP27A1) Enhances Cholesterol Efflux J. Biol. Chem., March 21, 2003; 278(13): 11015 - 11019. [Abstract] [Full Text] [PDF]

				S. Jabara, L. K. Christenson, C. Y. Wang, J. M. McAllister, N. B. Javitt, A. Dunaif, and J. F. Strauss III Stromal Cells of the Human Postmenopausal Ovary Display a Distinctive Biochemical and Molecular Phenotype J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 484 - 492. [Abstract] [Full Text] [PDF]