Am J Physiol Cell Physiol AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (September 5, 2001). doi:10.1152/ajpcell.00077.2001
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
281/6/C2010    most recent
00077.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sautin, Y. Y
Right arrow Articles by Svetlov, S. I
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sautin, Y. Y
Right arrow Articles by Svetlov, S. I

Articles in PresS, published online ahead of print September 5, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00077.2001
Submitted on February 15, 2001
Accepted on August 24, 2001

Enhancement of Survival by Lysophosphatidic Acid via Erk1/Erk2 and PI-3 kinase/Akt Pathways in a Murine Hepatocyte Cell Line

Yuri Y Sautin1, James M Crawford1, and Stanislav I Svetlov1*

1 Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, Florida, USA

* To whom correspondence should be addressed. E-mail: svetlov{at}pathology.ufl.edu.

Protective mechanisms for lysophosphatidic acid (LPA) against cell death caused by Clostridium difficile toxin, or TNF-{alpha} plus D-Galactosamine, were investigated in a murine hepatocyte cell line AML12 expressing Edg2 LPA receptor. In these models of hepatocellular injury, LPA prevented the hepatocyte damage, suppressed apoptosis, and enhanced cell survival in a dose-dependent fashion. The protective effects of LPA were abolished by wortmannin and LY294002, specific inhibitors of PI-3 kinase, and by PD98059 and U0126, inhibitors of MEK1/MEK2. In non-treated hepatocytes, LPA elicited a gradual and sustained increase in phosphorylation of Erk1/Erk2 over 180 min of stimulation, and downstream phosphorylation of p90RSK and transcription factor Elk-1. In Clostridium difficile toxin-treated cells, LPA-induced phosphorylation of Erk1/Erk2 was rapid but transient, while p90RSK and Elk-1 phosphorylation did not change significantly. LPA stimulated the phosphorylation of Akt in a time-dependent manner in both intact and toxin-treated AML12 hepatocytes. Wortmannin and LY294002 abolished the phosphorylation of Akt, further supporting activation of PI-3 kinase/Akt as a signaling pathway, which mediates hepatocyte protection by LPA. Taken together, these results demonstrate that LPA prevents cell apoptosis induced by Clostridium difficile toxin and TNF-{alpha}/D-Galactosamine in AML12 murine hepatocyte cell line. The cell protection by LPA involves the activation of MAP kinase Erk1/Erk2 cascade, and PI-3 kinase-dependent phosphorylation of Akt.




This article has been cited by other articles:


Home page
 Stem CellsHome page
J. Chen, A. R. Baydoun, R. Xu, L. Deng, X. Liu, W. Zhu, L. Shi, X. Cong, S. Hu, and X. Chen
Lysophosphatidic Acid Protects Mesenchymal Stem Cells Against Hypoxia and Serum Deprivation-Induced Apoptosis
Stem Cells, January 1, 2008; 26(1): 135 - 145.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
M. M. Murph, J. Hurst-Kennedy, V. Newton, D. N. Brindley, and H. Radhakrishna
Lysophosphatidic Acid Decreases the Nuclear Localization and Cellular Abundance of the p53 Tumor Suppressor in A549 Lung Carcinoma Cells
Mol. Cancer Res., November 1, 2007; 5(11): 1201 - 1211.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Bagga, K. S. Price, D. A. Lin, D. S. Friend, K. F. Austen, and J. A. Boyce
Lysophosphatidic acid accelerates the development of human mast cells
Blood, December 15, 2004; 104(13): 4080 - 4087.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Ikeda, K. Nagashima, M. Yanase, T. Tomiya, M. Arai, Y. Inoue, K. Tejima, T. Nishikawa, M. Omata, S. Kimura, et al.
Involvement of Rho/Rho kinase pathway in regulation of apoptosis in rat hepatic stellate cells
Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G880 - G886.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. D. Okusa, H. Ye, L. Huang, L. Sigismund, T. Macdonald, and K. R. Lynch
Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F565 - F574.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. Deng, D.-A. Wang, E. Gosmanova, L. R. Johnson, and G. Tigyi
LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway
Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G821 - G829.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. S. Liu, M. W. Musch, K. Sugi, M. M. Walsh-Reitz, M. J. Ropeleski, B. A. Hendrickson, C. Pothoulakis, J. T. Lamont, and E. B. Chang
Protective role of HSP72 against Clostridium difficile toxin A-induced intestinal epithelial cell dysfunction
Am J Physiol Cell Physiol, April 1, 2003; 284(4): C1073 - C1082.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.