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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions 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?

J Biol Chem, Vol. 274, Issue 28, 19707-19713, July 9, 1999

Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response

Riaz A. Memon, Walter M. Holleran, Yoshikazu Uchida, Arthur H. Moser, Shinichi Ichikawa, Yoshio Hirabayashi, Carl Grunfeld, and Kenneth R. Feingold

From the Departments of Medicine and Dermatology, University of California San Francisco, Metabolism Section, Medical Service and Dermatology Service, Department of Veterans Affairs Medical Center, San Francisco, California 94121 and the  Laboratory of Cellular Glycobiology, Frontier Research Program, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Saitama 351-0198, Japan

The host response to infection is associated with multiple alterations in lipid and lipoprotein metabolism. We have shown recently that endotoxin (lipopolysaccharide (LPS)) and cytokines enhance hepatic sphingolipid synthesis, increase the activity and mRNA levels of serine palmitoyltransferase, the first committed step in sphingolipid synthesis, and increase the content of sphingomyelin, ceramide, and glucosylceramide (GlcCer) in circulating lipoproteins in Syrian hamsters. Since the LPS-induced increase in GlcCer content of lipoproteins was far greater than that of ceramide or sphingomyelin, we have now examined the effect of LPS and cytokines on glycosphingolipid metabolism. LPS markedly increased the mRNA level of hepatic GlcCer synthase, the enzyme that catalyzes the first glycosylation step of glycosphingolipid synthesis. The LPS-induced increase in GlcCer synthase mRNA levels was seen within 2 h, sustained for 8 h, and declined to base line by 24 h. LPS-induced increase in GlcCer synthase mRNA was partly accounted for by an increase in its transcription rate. LPS produced a 3-4-fold increase in hepatic GlcCer synthase activity and significantly increased the content of GlcCer (the immediate product of GlcCer synthase reaction) as well as ceramide trihexoside and ganglioside GM3 (products distal to the GlcCer synthase step) in the liver. Moreover, both tumor necrosis factor- and interleukin-1, cytokines that mediate many of the metabolic effects of LPS, increased hepatic GlcCer synthase mRNA levels in vivo as well as in HepG2 cells in vitro, suggesting that these cytokines can directly stimulate glycosphingolipid metabolism. These results indicate that LPS and cytokines up-regulate glycosphingolipid metabolism in vivo and in vitro. An increase in GlcCer synthase mRNA levels and activity leads to the increase in hepatic GlcCer content and may account for the increased GlcCer content in circulating lipoproteins during the acute phase response.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				N. V. Giltiay, A. A. Karakashian, A. P. Alimov, S. Ligthle, and M. N. Nikolova-Karakashian Ceramide- and ERK-dependent pathway for the activation of CCAAT/enhancer binding protein by interleukin-1{beta} in hepatocytes J. Lipid Res., November 1, 2005; 46(11): 2497 - 2505. [Abstract] [Full Text] [PDF]

				A. Kohyama-Koganeya, T. Sasamura, E. Oshima, E. Suzuki, S. Nishihara, R. Ueda, and Y. Hirabayashi Drosophila Glucosylceramide Synthase: A NEGATIVE REGULATOR OF CELL DEATH MEDIATED BY PROAPOPTOTIC FACTORS J. Biol. Chem., August 20, 2004; 279(34): 35995 - 36002. [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]

				Y. Uchida, S. Murata, M. Schmuth, M. J. Behne, J. D. Lee, S. Ichikawa, P. M. Elias, Y. Hirabayashi, and W. M. Holleran Glucosylceramide synthesis and synthase expression protect against ceramide-induced stress J. Lipid Res., August 1, 2002; 43(8): 1293 - 1302. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines J. Lipid Res., October 1, 2001; 42(10): 1636 - 1644. [Abstract] [Full Text] [PDF]

				R. A. Memon, W. M. Holleran, Y. Uchida, A. H. Moser, C. Grunfeld, and K. R. Feingold Regulation of sphingolipid and glycosphingolipid metabolism in extrahepatic tissues by endotoxin J. Lipid Res., March 1, 2001; 42(3): 452 - 459. [Abstract] [Full Text]

				S. A. Boldin and A. H. Futerman Up-regulation of Glucosylceramide Synthesis upon Stimulation of Axonal Growth by Basic Fibroblast Growth Factor. EVIDENCE FOR POST-TRANSLATIONAL MODIFICATION OF GLUCOSYLCERAMIDE SYNTHASE J. Biol. Chem., March 31, 2000; 275(14): 9905 - 9909. [Abstract] [Full Text] [PDF]