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

Nagadhara Dronadula, Farhan Rizvi, Eva Blaskova, Quanyi Li, Rao Gadiparthi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 F, 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.

Original languageEnglish (US)
Pages (from-to)767-777
Number of pages11
JournalJournal of lipid research
Volume47
Issue number4
DOIs
StatePublished - Apr 1 2006

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Cyclic AMP Response Element-Binding Protein
Vascular Smooth Muscle
Arachidonic Acid
Smooth Muscle Myocytes
Cell Movement
Muscle
Cells
Prostaglandin-Endoperoxide Synthases
Lipoxygenase
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Phosphorylation
Chemical activation
Metabolites
Arachidonate 15-Lipoxygenase
Hydroxyeicosatetraenoic Acids
Dinoprost
Eicosanoids
Protein-Serine-Threonine Kinases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility. / Dronadula, Nagadhara; Rizvi, Farhan; Blaskova, Eva; Li, Quanyi; Gadiparthi, Rao.

In: Journal of lipid research, Vol. 47, No. 4, 01.04.2006, p. 767-777.

Research output: Contribution to journalArticle

Dronadula, Nagadhara ; Rizvi, Farhan ; Blaskova, Eva ; Li, Quanyi ; Gadiparthi, Rao. / Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility. In: Journal of lipid research. 2006 ; Vol. 47, No. 4. pp. 767-777.
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AB - 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 F2α, 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.

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