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 Spitsen, G. M. Articles by Davis, R. A. Search for Related Content PubMed PubMed Citation Articles by Spitsen, G. M. Articles by Davis, R. A. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 1347-1355, August 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

In nonhepatic cells, cholesterol 7-hydroxylase induces the expression of genes regulating cholesterol biosynthesis, efflux, and homeostasis

Correspondence to: Roger A. Davis

CHO cells expressing the liver-specific gene product cholesterol-7-hydroxylase showed a 6-fold increase in the biosynthesis of [¹⁴C]cholesterol from [¹⁴C]acetate, as well as increased enzymatic activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and squalene synthase. Cells expressing cholesterol-7-hydroxylase contained less sterol response element-binding protein 1 (SREBP1) precursor, whereas the cellular content of mature SREBP1, as well as the mRNAs of cholesterol biosynthetic genes (HMG-CoA reductase and squalene synthase), were all increased 3-fold. Cells expressing cholesterol-7-hydroxylase displayed greater activities of luciferase reporters containing the SREBP-dependent promoter elements derived from HMG-CoA reductase and farnesyl diphosphate synthase, in spite of accumulating significantly more free and esterified cholesterol and 7-hydroxycholesterol. While cells expressing cholesterol-7-hydroxylase displayed increased SREBP-dependent transcription, sterol-mediated repression of SREBP-dependent transcription by LDL-cholesterol and exogenous oxysterols was similar in both cell types. Cells expressing cholesterol-7-hydroxylase displayed greater rates of secretion of cholesterol as well as increased expression of the ABC1 cassette protein mRNA. Adding 25-hydroxycholesterol to the culture medium of both cell types increased the expression of ABC1 cassette protein mRNA.

The combined data suggest that in nonhepatic CHO cells multiple regulatory processes sensitive to cellular sterols act independently to coordinately maintain cellular cholesterol homeostasis.—Spitsen, G. M., S. Dueland, S. K. Krisans, C. J. Slattery, J. H. Miyake, and R. A. Davis. In nonhepatic cells, cholesterol-7-hydroxylase induces the expression of genes regulating cholesterol biosynthesis, efflux, and homeostasis. J. Lipid Res. 2000. 41: 1347;–1355.

Supplementary key words: cholesterol, sterol regulation, oxysterols, 7-hydroxylase

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

This article has been cited by other articles:

				E. P. Ratliff, A. Gutierrez, and R. A. Davis Transgenic expression of CYP7A1 in LDL receptor-deficient mice blocks diet-induced hypercholesterolemia J. Lipid Res., July 1, 2006; 47(7): 1513 - 1520. [Abstract] [Full Text] [PDF]

				R. A. Davis, J. H. Miyake, T. Y. Hui, and N. J. Spann Regulation of cholesterol-7{alpha}-hydroxylase: BAREly missing a SHP J. Lipid Res., April 1, 2002; 43(4): 533 - 543. [Abstract] [Full Text] [PDF]

				G. L. Moore and R. A. Davis Expression of cholesterol-7{alpha}-hydroxylase in murine macrophages prevents cholesterol loading by acetyl-LDL J. Lipid Res., April 1, 2002; 43(4): 629 - 635. [Abstract] [Full Text] [PDF]

				J. H. Miyake, X. T. Duong-Polk, J. M. Taylor, E. Z. Du, L. W. Castellani, A. J. Lusis, and R. A. Davis Transgenic Expression of Cholesterol-7-{alpha}-Hydroxylase Prevents Atherosclerosis in C57BL/6J Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 121 - 126. [Abstract] [Full Text] [PDF]

				A. B. Reiss, N. W. Awadallah, S. Malhotra, M. C. Montesinos, E. S. L. Chan, N. B. Javitt, and B. N. Cronstein Immune complexes and IFN-{gamma} decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages J. Lipid Res., November 1, 2001; 42(11): 1913 - 1922. [Abstract] [Full Text] [PDF]

				W. M. Pandak, C. Schwarz, P. B. Hylemon, D. Mallonee, K. Valerie, D. M. Heuman, R. A. Fisher, K. Redford, and Z. R. Vlahcevic Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G878 - G889. [Abstract] [Full Text] [PDF]

				R. A. Davis and T. Y. Hui 2000 George Lyman Duff Memorial Lecture : Atherosclerosis Is a Liver Disease of the Heart Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 887 - 898. [Abstract] [Full Text] [PDF]