J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on January 1, 2005

Papers In Press, published online ahead of print November 1, 2004
J. Lipid Res., doi:10.1194/jlr.M400219-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M400219-JLR200v1
46/1/76    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dubrac, S.
Right arrow Articles by Erickson, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dubrac, S.
Right arrow Articles by Erickson, S. K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Submitted on June 14, 2004
Revised on October 18, 2004
Accepted on October 18, 2004

Role of CYP27A in cholesterol and bile acid metabolism

Sandrine Dubrac, Steven R. Lear, Meena Ananthanarayanan, Natarajan Balasubramaniyan, Jaya Bollineni, Sarah Shefer, Hideyuki Hyogo, David E. Cohen, Patricia J. Blanche, Ronald M. Krauss, Ashok K. Batta, Gerald Salen, Frederick J. Suchy, Nobuyo Maeda, and Sandra K. Erickson

VAMC-111F, San Francisco, CA 94121

Corresponding Author: skerick{at}itsa.ucsf.edu

The CYP27A gene encodes a mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase, that is expressed in many different tissues and plays an important role in cholesterol and bile acid metabolism. In humans, CYP27A deficiency leads to cerebrotendinous xanthomatosis. To gain insight into roles of CYP27A in regulation of cholesterol and bile acid metabolism, cyp27A gene knockout heterozygous, homozygous and wild type littermate mice were studied. In contrast to homozygotes, heterozygotes had increased body weights and were mildly hypercholesterolemic with increased numbers of lipoprotein particles in the low density lipoprotein size range. Cyp7A expression was not increased in heterozygotes, but it was in homozygotes suggesting parts of the homozygous phenotype are secondary to increased cyp7A expression and activity. Homozygotes exhibited pronounced hepatomegaly and dysregulation in hepatic cholesterol, bile acid and fatty acid metabolism. Hepatic cholesterol synthesis and synthesis of bile acid intermediates were elevated; however, side chain cleavage was impaired leading to decreased bile salt concentrations in gallbladder bile. Expression of Ntcp, the major sinusoidal bile salt transporter was increased and that of Bsep, the major canalicular bile salt transporter, decreased. Gender played a modifying role in homozygous response to cyp27A deficiency, with females being generally more severely impacted. Thus, both cyp27A genotype and gender impacted regulation of hepatic bile acid, cholesterol and fatty acid metabolism.


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


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
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]

Home page
 Physiol. Rev.Home page
E. Ikonen
Mechanisms for cellular cholesterol transport: defects and human disease.
Physiol Rev, October 1, 2006; 86(4): 1237 - 1261.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
X. Li, P. Hylemon, W. M. Pandak, and S. Ren
Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria
J. Lipid Res., July 1, 2006; 47(7): 1507 - 1512.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.