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

This Article 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 Memon, R. A. Articles by Feingold, K. R. Search for Related Content PubMed PubMed Citation Articles by Memon, R. A. Articles by Feingold, K. R. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 38, 1620-1629, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Endotoxin, tumor necrosis factor, and interleukin-1 decrease hepatic squalene synthase activity, protein, and mRNA levels in Syrian hamsters

RA Memon, I Shechter, AH Moser, JK Shigenaga, C Grunfeld and KR Feingold
Department of Medicine, University of California San Francisco, and Department of Veterans Affairs Medical Center, 94121, USA.

Recent studies have shown that endotoxin (LPS) administration to Syrian hamsters markedly increased hepatic HMG-CoA reductase activity, protein mass, and mRNA levels, but only produced a modest increase in hepatic cholesterol synthesis, suggesting that LPS may also influence other key enzymes involved in the regulation of cholesterol metabolism. In the present study, we have examined the effect of LPS and cytokines on the activity, protein mass, and mRNA level of squalene synthase, which is the first committed enzyme in cholesterol biosynthesis and is located at a branch point in the mevalonate pathway. Our results demonstrate that LPS administration produces a marked decrease in the mRNA levels of squalene synthase. This decrease in squalene synthase mRNA occurred very rapidly (90 min after LPS) and required relatively small doses of LPS (1 microg/100 gm body weight). LPS also significantly decreased squalene synthase activity and protein mass. Finally, LPS produced a marked decrease in squalene synthase mRNA, activity, and protein levels when the basal levels of squalene synthase expression were increased 4- fold by prior treatment with bile acid binding resin, colestipol. Tumor necrosis factor and interleukin-1, which mediate many of the metabolic effects of LPS, also decreased hepatic squalene synthase activity and mRNA levels. Taken together, our results suggest that the discordant regulation of HMG-CoA reductase and squalene synthase during the host response to infection and inflammation may have substantial effects on the regulation of substrate flux into the non-sterol pathways of mevalonate metabolism.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. F. Tacer, D. Kuzman, M. Seliskar, D. Pompon, and D. Rozman TNF-{alpha} interferes with lipid homeostasis and activates acute and proatherogenic processes Physiol Genomics, October 19, 2007; 31(2): 216 - 227. [Abstract] [Full Text] [PDF]

				C. Popa, M. G. Netea, P. L. C. M. van Riel, J. W. M. van der Meer, and A. F. H. Stalenhoef The role of TNF-{alpha} in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk J. Lipid Res., April 1, 2007; 48(4): 751 - 762. [Abstract] [Full Text] [PDF]

				H. Okazaki, F. Tazoe, S. Okazaki, N. Isoo, K. Tsukamoto, M. Sekiya, N. Yahagi, Y. Iizuka, K. Ohashi, T. Kitamine, et al. Increased cholesterol biosynthesis and hypercholesterolemia in mice overexpressing squalene synthase in the liver J. Lipid Res., September 1, 2006; 47(9): 1950 - 1958. [Abstract] [Full Text] [PDF]

				P. Aspichueta, B. Perez-Agote, S. Perez, B. Ochoa, and O. Fresnedo Impaired response of VLDL lipid and apoB secretion to endotoxin in the fasted rat liver Innate Immunity, June 1, 2006; 12(3): 181 - 191. [Abstract] [PDF]

				S. E. Dunn, S. Youssef, M. J. Goldstein, T. Prod'homme, M. S. Weber, S. S. Zamvil, and L. Steinman Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin J. Exp. Med., February 21, 2006; 203(2): 401 - 412. [Abstract] [Full Text] [PDF]

				M. B. Fessler, S. K. Young, S. Jeyaseelan, J. G. Lieber, P. G. Arndt, J. A. Nick, and G. S. Worthen A Role for Hydroxy-Methylglutaryl Coenzyme A Reductase in Pulmonary Inflammation and Host Defense Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 606 - 615. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]

				J.-Y. Yoo and S. Desiderio Innate and acquired immunity intersect in a global view of the acute-phase response PNAS, February 4, 2003; 100(3): 1157 - 1162. [Abstract] [Full Text] [PDF]

				R. J. Cenedella, J. R. Kuszak, K. J. Al-Ghoul, S. Qin, and P. S. Sexton Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats J. Lipid Res., January 1, 2003; 44(1): 198 - 211. [Abstract] [Full Text] [PDF]

				S. M. Houten, J. Frenkel, G. T. Rijkers, R. J.A. Wanders, W. Kuis, and H. R. Waterham Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in Hyper-IgD and periodic fever syndrome Hum. Mol. Genet., December 1, 2002; 11(25): 3115 - 3124. [Abstract] [Full Text] [PDF]

				R. A. Memon, W. M. Holleran, A. H. Moser, T. Seki, Y. Uchida, J. Fuller, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Endotoxin and Cytokines Increase Hepatic Sphingolipid Biosynthesis and Produce Lipoproteins Enriched in Ceramides and Sphingomyelin Arterioscler. Thromb. Vasc. Biol., August 1, 1998; 18(8): 1257 - 1265. [Abstract] [Full Text] [PDF]

				A. P. Beigneux, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold The Acute Phase Response Is Associated with Retinoid X Receptor Repression in Rodent Liver J. Biol. Chem., May 19, 2000; 275(21): 16390 - 16399. [Abstract] [Full Text] [PDF]

				R. A. Memon, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold In Vivo and in Vitro Regulation of Sterol 27-Hydroxylase in the Liver during the Acute Phase Response. POTENTIAL ROLE OF HEPATOCYTE NUCLEAR FACTOR-1 J. Biol. Chem., August 3, 2001; 276(32): 30118 - 30126. [Abstract] [Full Text] [PDF]