A Requirement for Calcium-independent Phospholipase A2 in Thrombin-induced Arachidonic Acid Release and Growth in Vascular Smooth Muscle Cells

Chandrahasa R. Yellaturu, Rao Gadiparthi

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Abstract

Thrombin is a potent mitogen for vascular smooth muscle cells (VSMC). To understand its mitogenic signaling events, we have studied the role of calcium-independent phospholipase A2 (iPLA2). Without affecting its levels, thrombin increased iPLA2 activity in a time-dependent manner in VSMC. Thrombin also induced arachidonic acid release and DNA synthesis by about 2-fold as compared with control. Down-regulation of iPLA2 activity by its specific inhibitor, bromoenol lactone, or its expression by antisense oligonucleotides, significantly reduced thrombin-induced arachidonic acid release and DNA synthesis in VSMC. To learn the mechanism of thrombin-stimulated iPLA2 activity, we next tested the role of p38 MAPK. Thrombin stimulated p38 MAPK phosphorylation and activity in a time-dependent manner in VSMC. Inhibition of p38 MAPK activity by SB203580 and SB202190 resulted in decreased iPLA2 activity, arachidonic acid release, and DNA synthesis induced by thrombin in VSMC. Together, these results for the first time demonstrate that iPLA2 plays a role in thrombin-induced arachidonic acid release and growth in VSMC and that these responses are mediated by p38 MAPK.

Original languageEnglish (US)
Pages (from-to)43831-43837
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number44
DOIs
StatePublished - Oct 31 2003

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Calcium-Independent Phospholipase A2
Vascular Smooth Muscle
Arachidonic Acid
Thrombin
Smooth Muscle Myocytes
Muscle
Cells
Phospholipases A2
p38 Mitogen-Activated Protein Kinases
Growth
DNA
Phosphorylation
Antisense Oligonucleotides
Mitogens
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

A Requirement for Calcium-independent Phospholipase A2 in Thrombin-induced Arachidonic Acid Release and Growth in Vascular Smooth Muscle Cells. / Yellaturu, Chandrahasa R.; Gadiparthi, Rao.

In: Journal of Biological Chemistry, Vol. 278, No. 44, 31.10.2003, p. 43831-43837.

Research output: Contribution to journalArticle

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