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

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

Journal of Lipid Research, Vol. 43, 665-670, May 2002
Copyright © 2002 by Lipid Research, Inc.

Review

25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles

Norman B. Javitt¹

Department of Pediatrics and Medicine, NYU School of Medicine, New York, NY 10016

¹ e-mail norman.javitt{at}med.nyu.edu

The CYP27 gene is expressed in arterial endothelium, macrophages, and other tissues. The gene product generates sterol intermediates that function as ligands for nuclear receptors prior to their transport to the liver for metabolism, mostly to bile acids. Most attention has been given to 27-hydroxycholesterol as a ligand for LXR activated receptors and to chenodeoxycholic acid as a ligand for farnesoid X activated receptors (FXRs). Expression of the pathway in macrophages is essential for normal reverse cholesterol transport. Thus, ABC transporter activity is upregulated, which enhances cholesterol efflux. Absence of these mechanisms probably accounts for the accelerated atherosclerosis that occurs in cerebrotendinous xanthomatosis. Accumulation of 27-hydroxycholesterol in human atheroma is puzzling and may reflect low levels of oxysterol 7-hydroxylase activity in human macrophages. The same enzyme determines the proportion of mono-, di-, and tri-hydroxy bile acids synthesized in the liver. Oxysterol 7-hydroxylase deficiency is a molecular basis for cholestatic liver disease. Chenodeoxycholic acid, the major normal end product, downregulates expression of cholesterol 7-hydroxylase via the FXR/short heterodimer protein nuclear receptor and thus limits total bile acid production. The challenge is to quantify in a physiologic setting the magnitude of the pathway in different tissues and to further evaluate the biologic roles of all the intermediates that may function as ligands for orphan nuclear receptors or via other regulatory mechanisms.—Javitt, N. B. 25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles. J. Lipid Res. 2002. 43: 665–670.

Abbreviations: StAR, steroid acute response

Supplementary key words CYP27 • CYP7A • CYP7B • ABC transporter • monohydroxy bile acids • StAR • cholestasis • atheroma

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Fuda, N. B. Javitt, K. Mitamura, S. Ikegawa, and C. A. Strott Oxysterols are substrates for cholesterol sulfotransferase J. Lipid Res., June 1, 2007; 48(6): 1343 - 1352. [Abstract] [Full Text] [PDF]

				S. Ren, P. Hylemon, Z.-P. Zhang, D. Rodriguez-Agudo, D. Marques, X. Li, H. Zhou, G. Gil, and W. M. Pandak Identification of a novel sulfonated oxysterol, 5-cholesten-3{beta},25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria J. Lipid Res., May 1, 2006; 47(5): 1081 - 1090. [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. Meaney Is C-26 hydroxylation an evolutionarily conserved steroid inactivation mechanism? FASEB J, August 1, 2005; 19(10): 1220 - 1224. [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]

				T. Nishimaki-Mogami, M. Une, T. Fujino, Y. Sato, N. Tamehiro, Y. Kawahara, K. Shudo, and K. Inoue Identification of intermediates in the bile acid synthetic pathway as ligands for the farnesoid X receptor J. Lipid Res., August 1, 2004; 45(8): 1538 - 1545. [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]