Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells

Rao Gadiparthi, A. S. Baas, W. C. Glasgow, T. E. Eling, M. S. Runge, R. W. Alexander

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Previous studies from this laboratory and others suggest that arachidonic acid and its metabolites play important roles in a variety of biological processes such as signal transduction, contraction, chemotaxis, and cell growth and differentiation. Here we studied the effect of arachidonic acid an mitogen-activated protein (MAP) kinases in vascular smooth muscle cells (VSMC). Arachidonic acid activated MAP kinases in VSMC in a time- and dose- dependent manner. Nordihydroguaiaretic acid (NDGA), a potent inhibitor of the lipoxygenase system, significantly blocked the arachidonic acid-induced activation of MAP kinases, whereas indomethacin, an inhibitor of cyclooxygenase, had no effect. In VSMC, arachidonic acid was converted to 15- hydroxyeicosatetraenoic acid (15-HETE); NDGA inhibited the formation of this HETE. Exogenous addition of 15-HETE to VSMC caused stimulation of MAP kinases. Depletion of protein kinase C attenuated both the arachidonic acid- and 15-HETE-induced activation of MAP kinases in VSMC. Together these results suggest that 1) arachidonic acid activates MAP kinases in VSMC; 2) 15-HETE, a 15-lipoxygenase product of arachidonic acid, at least in part, mediates the arachidonic acid effect on MAP kinases; and 3) protein kinase C appears to be important in arachidonic acid activation of MAP kinases. Therefore, MAP kinases may play an important role in arachidonic acid signaling of VSMC growth and function.

Original languageEnglish (US)
Pages (from-to)32586-32591
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number51
StatePublished - 1994
Externally publishedYes

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Metabolites
Mitogen-Activated Protein Kinases
Vascular Smooth Muscle
Arachidonic Acid
Smooth Muscle Myocytes
Muscle
Chemical activation
Cells
Hydroxyeicosatetraenoic Acids
Masoprocol
Cell growth
Protein Kinase C
Arachidonate 15-Lipoxygenase
Biological Phenomena
Lipoxygenase Inhibitors
Cyclooxygenase Inhibitors
Signal transduction
Chemotaxis
Growth
Indomethacin

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Gadiparthi, R., Baas, A. S., Glasgow, W. C., Eling, T. E., Runge, M. S., & Alexander, R. W. (1994). Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. Journal of Biological Chemistry, 269(51), 32586-32591.

Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. / Gadiparthi, Rao; Baas, A. S.; Glasgow, W. C.; Eling, T. E.; Runge, M. S.; Alexander, R. W.

In: Journal of Biological Chemistry, Vol. 269, No. 51, 1994, p. 32586-32591.

Research output: Contribution to journalArticle

Gadiparthi, Rao ; Baas, A. S. ; Glasgow, W. C. ; Eling, T. E. ; Runge, M. S. ; Alexander, R. W. / Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 51. pp. 32586-32591.
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