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) All Versions of this Article: M500369-JLR200v1 47/4/767    most recent Alert me when this article is cited 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 Dronadula, N. Articles by Rao, G. N. Search for Related Content PubMed PubMed Citation Articles by Dronadula, N. Articles by Rao, G. N. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 767-777, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility

Nagadhara Dronadula, Farhan Rizvi¹, Eva Blaskova¹, Quanyi Li and Gadiparthi N. Rao²

Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163

Published, JLR Papers in Press, December 28, 2006.

¹ F. Rizvi and E. Blaskova contributed equally to this work.

² To whom correspondence should be addressed. e-mail: grao{at}physio1.utmem.edu

In addition to their role in many vital cellular functions, arachidonic acid (AA) and its eicosanoid metabolites are involved in the pathogenesis of several diseases, including atherosclerosis and cancer. To understand the potential mechanisms by which these lipid molecules could influence the disease processes, particularly cardiovascular diseases, we studied AA's effects on vascular smooth muscle cell (VSMC) motility and the role of cAMP-response element binding protein-1 (CREB-1) in this process. AA exerted differential effects on VSMC motility; at lower doses, it stimulated motility, whereas at higher doses, it was inhibitory. AA-induced VSMC motility requires its conversion via the lipoxygenase (LOX) and cyclooxygenase (COX) pathways. AA stimulated the phosphorylation of extracellular signal-regulated kinases (ERKs), Jun N-terminal kinases (JNKs), and p38 mitogen-activated protein kinase (p38MAPK) in a time-dependent manner, and blockade of these serine/threonine kinases significantly attenuated AA-induced VSMC motility. In addition, AA stimulated CREB-1 phosphorylation and activity in a manner that was also dependent on its metabolic conversion via the LOX and COX pathways and the activation of ERKs and p38MAPK but not JNKs. Furthermore, suppression of CREB-1 activation inhibited AA-induced VSMC motility. 15(S)-Hydroxyeicosatetraenoic acid and prostaglandin F₂, the 15-LOX and COX metabolites of AA, respectively, that are produced by VSMC at lower doses, were also found to stimulate motility in these cells. Together, these results suggest that AA induces VSMC motility by complex mechanisms involving its metabolism via the LOX and COX pathways as well as the ERK- and p38MAPK-dependent and JNK-independent activation of CREB-1.

Supplementary key words cell migration • adenosine 3',5'-cyclic monophosphate • cyclooxygenase • fatty acid • lipoxygenase • mitogen-activated protein kinases

Abbreviations: AA, arachidonic acid; COX, cyclooxygenase; CREB-1, cAMP-response element binding protein-1; CYP, cytochrome P450; ERK, extracellular signal-regulated kinase; ETI, 5,8,11-eicosatriynoic acid; HETE, hydroxyeicosatetraenoic acid; JNK, Jun N-terminal kinase; LOX, lipoxygenase; PGF₂, prostaglandin F₂; p38MAPK, p38 mitogen-activated protein kinase; VSMC, vascular smooth muscle cell

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. R. Chava, M. Karpurapu, D. Wang, M. Bhanoori, V. Kundumani-Sridharan, Q. Zhang, T. Ichiki, W. C. Glasgow, and G. N. Rao CREB-Mediated IL-6 Expression Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-Induced Vascular Smooth Muscle Cell Migration Arterioscler. Thromb. Vasc. Biol., June 1, 2009; 29(6): 809 - 815. [Abstract] [Full Text] [PDF]

				M. A. Reddy, S. Sahar, L. M. Villeneuve, L. Lanting, and R. Natarajan Role of Src Tyrosine Kinase in the Atherogenic Effects of the 12/15-Lipoxygenase Pathway in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., March 1, 2009; 29(3): 387 - 393. [Abstract] [Full Text] [PDF]

				A. K. Bajpai, E. Blaskova, S. B. Pakala, T. Zhao, W. C. Glasgow, J. S. Penn, D. A. Johnson, and G. N. Rao 15(S)-HETE Production in Human Retinal Microvascular Endothelial Cells by Hypoxia: Novel Role for MEK1 in 15(S)-HETE Induced Angiogenesis Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 4930 - 4938. [Abstract] [Full Text] [PDF]

				Z. Xie, M. C. Gong, W. Su, J. Turk, and Z. Guo Group VIA Phospholipase A2 (iPLA2beta) Participates in Angiotensin II-induced Transcriptional Up-regulation of Regulator of G-protein Signaling-2 in Vascular Smooth Muscle Cells J. Biol. Chem., August 31, 2007; 282(35): 25278 - 25289. [Abstract] [Full Text] [PDF]

				D. Wang, Z. Liu, Q. Li, M. Karpurapu, V. Kundumani-Sridharan, H. Cao, N. Dronadula, F. Rizvi, A. K. Bajpai, C. Zhang, et al. An Essential Role for gp130 in Neointima Formation Following Arterial Injury Circ. Res., March 30, 2007; 100(6): 807 - 816. [Abstract] [Full Text] [PDF]