J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print July 1, 2003
J. Lipid Res., doi:10.1194/jlr.M200487-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M200487-JLR200v1
44/10/1859    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 Tran, H.
Right arrow Articles by Strickland, D. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tran, H.
Right arrow Articles by Strickland, D. 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 December 26, 2002
Revised on June 9, 2003
Accepted on June 27, 2003

Modulation of the LDL receptor and LRP levels by HIV protease inhibitors

Huan Tran, Susan Robinson, Irina Mikhailenko, and Dudley K. Strickland

Department of Vascular Biology, J. Holland Laboratory, American Red Cross, Rockville, MD 20855

Corresponding Author: strickla{at}usa.redcross.org

Inhibitors of the HIV-1 protease have proven to be effective anti-retroviral drugs. However, patients receiving HIV protease inhibitors develop serious metabolic abnormalities characterized by a peripheral lipodystrophy syndrome, insulin resistance, hypertriglyceridemia, and hypercholesterolemia resulting from elevated LDL levels. The objective of the present study was to identify mechanisms by which HIV protease inhibitors increase plasma cholesterol levels. Plasma LDL levels are regulated by a balance between biosynthetic and clearance pathways which involves removal of LDL from the plasma mediated by the hepatic LDL receptor. We hypothesized that HIV protease inhibitors may effect gene regulation of certain LDL receptor family members. In this present study we investigated the effect of several HIV protease inhibitors (ABT-378, Amprenavir, Indinavir, Nelfinavir, Ritonavir, and Saquinavir) on mRNA, protein, and functional levels of the LDL receptor and other LDL receptor family members. Our results demonstrate that one of these drugs, Nelfinavir significantly decreases LDL receptor and the LDL receptor-related protein (LRP) mRNA and protein levels, resulting in reduced functional activity of these two receptors. Nelfinavir exerts its effect by reducing levels of active SREBP1 in the nucleus. The findings that Nelfinavir reduces the levels of two key receptors (LRP and LDL receptor) involved in lipoprotein catabolism and maintenance of vessel wall integrity identifies a mechanism causing hypercholesterolemia complications present in HIV patients treated with this drug and raises concerns about the atherogenic nature of Nelfinavir.


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. Nutr.Home page
E. S. Shin, H. H. Lee, S. Y. Cho, H. W. Park, S. J. Lee, and T. R. Lee
Genistein Downregulates SREBP-1 Regulated Gene Expression by Inhibiting Site-1 Protease Expression in HepG2 Cells
J. Nutr., May 1, 2007; 137(5): 1127 - 1131.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H. Zhou, W. M. Pandak Jr., V. Lyall, R. Natarajan, and P. B. Hylemon
HIV Protease Inhibitors Activate the Unfolded Protein Response in Macrophages: Implication for Atherosclerosis and Cardiovascular Disease
Mol. Pharmacol., September 1, 2005; 68(3): 690 - 700.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.