AJP - Lung AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 281: L108-L118, 2001;
1040-0605/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Awasthi, S.
Right arrow Articles by King, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Awasthi, S.
Right arrow Articles by King, R. J.
Vol. 281, Issue 1, L108-L118, July 2001

CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-alpha , p38 MAPK, cPLA2, and 5-lipoxygenase

Shanjana Awasthi, Jeevalatha Vivekananda, Vibhudutta Awasthi, Dolphin Smith, and Richard J. King

Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900

In a companion paper (Vivekananda J, Smith D, and King RJ. Am J Physiol Lung Cell Mol Physiol 281: L98-L107, 2001), we demonstrated that tumor necrosis factor (TNF)-alpha inhibited the activity of CTP:phosphocholine cytidylyltransferase (CT), the rate-limiting enzyme in the de novo synthesis of phosphatidylcholine (PC), and that its actions were likely exerted through a metabolite of sphingomyelin. In this paper, we explore the signaling pathway employed by TNF-alpha using C2 ceramide as a cell-penetrating sphingolipid representative of the metabolites induced by TNF-alpha . We found that in H441 cells, as reported in other cell types, cytosolic phospholipase A2 (cPLA2) is activated by TNF-alpha . We also observed that the inhibiting action of C2 ceramide on CT requires protein kinase C-alpha , p38 mitogen-activated protein kinase, and cPLA2. The actions of C2 ceramide on CT activity can be duplicated by adding 2 µM lysoPC to these cells. Furthermore, we found that the effects of C2 ceramide are dependent on 5-lipoxygenase but that cyclooxygenase II is unimportant. We hypothesize that CT activity is inhibited by the lysoPC generated as a consequence of the activation of cPLA2 by protein kinase C-alpha and p38 mitogen-activated protein kinase. The other product of the activation of cPLA2, arachidonic acid, is a substrate for the synthesis of leukotrienes, which raise intracellular Ca2+ levels and complete the activation of cPLA2.

lung injury; pulmonary surfactant; phosphatidylcholine synthesis; leukotrienes; cytidine 5'-triphosphate; protein kinase C; mitogen-activated protein kinase; cytosolic phospholipase A2


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. Sparkman, H. Chandru, and V. Boggaram
Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L351 - L358.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. J. Ryan, D. M. McCoy, S. E. McGowan, R. G. Salome, and R. K. Mallampalli
Alveolar sphingolipids generated in response to TNF-alpha modifies surfactant biophysical activity
J Appl Physiol, January 1, 2003; 94(1): 253 - 258.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
B. Ramos, M. E. Mouedden, E. Claro, and S. Jackowski
Inhibition of CTP:Phosphocholine Cytidylyltransferase by C2-Ceramide and Its Relationship to Apoptosis
Mol. Pharmacol., November 1, 2002; 62(5): 1068 - 1075.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
O. L. Miakotina and J. M. Snyder
TNF-alpha inhibits SP-A gene expression in lung epithelial cells via p38 MAPK
Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L418 - L427.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Vivekananda, D. Smith, and R. J. King
Sphingomyelin metabolites inhibit sphingomyelin synthase and CTP:phosphocholine cytidylyltransferase
Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L98 - L107.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online