|
|
||||||||
AJP - Cell Physiology, Vol 262, Issue 2 C328-C338, Copyright © 1992 by American Physiological Society
ARTICLES |
S. L. Bursten, W. E. Harris, K. Resch and D. H. Lovett
Department of Medicine, Seattle Veterans Affairs Medical Center, University of Washington 98108.
Lipid A, the active component of bacterial endotoxin, stimulates multiple cell types, including glomerular mesangial cells (MC), and yet the molecular mechanisms of cell activation remain unclear. Lipid A, in its monosaccharyl form, structurally resembles the biologically active lipid phosphatidic acid (PA). Given this, it was postulated that lipid A activates cells by acting as a structural and functional mimetic of PA. Lipid A was found to specifically stimulate an MC lyso-PA acyl transferase activity, leading to enhanced synthesis of sn-2-unsaturated forms of PA. Sn-2-unsaturated PA itself, in contrast to sn-2-saturated PA, also stimulated the lyso-PA acyl transferase activity, a positive feedback feature previously noted with lyso-lecithin acyl transferase. Structure-function correlations demonstrated that the phosphate moieties in both PA and lipid A were necessary to feedback stimulation of lyso-PA acyl transferase (AT), as dephosphorylated lipid A and 2-unsaturated 1,2-sn-diacylglycerol had no stimulatory effect on lyso-PA AT. The biologic relevance of the lipid A and PA-mediated increases in lyso-PA acyl transferase activity was shown, whereby limited exposure to these lipids rapidly induced identical MC morphologic and functional alterations characteristic of cellular activation. By mimicking the stimulatory action of PA, per se, on lyso-PA acyl transferase activity, lipid A may initiate a positive feedback cycle of acylation, yielding increased amounts of PA enriched in unsaturated fatty acids. This newly synthesized PA may subsequently act as the proximal mediator of cellular activation.
This article has been cited by other articles:
![]() |
B. Aguado and R. D. Campbell Characterization of a Human Lysophosphatidic Acid Acyltransferase That Is Encoded by a Gene Located in the Class III Region of the Human Major Histocompatibility Complex J. Biol. Chem., February 13, 1998; 273(7): 4096 - 4105. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Eberhardt, P. W. Gray, and L. W. Tjoelker Human Lysophosphatidic Acid Acyltransferase. cDNA CLONING, EXPRESSION, AND LOCALIZATION TO CHROMOSOME 9q34.3 J. Biol. Chem., August 8, 1997; 272(32): 20299 - 20305. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |