Role of 15-hydroxyeicosatetraenoic acid in phosphorylation of ERK1/2 and caldesmon in pulmonary arterial smooth muscle cells.

Abstract

We have reported that 15-hydroxyeicosatetraenoic acid (15-HETE) induces pulmonary artery (PA) contraction in rats exposed to hypoxia by activating extracellular signal-regulated kinase 1/2 (ERK1/2). In this study, we investigated the characteristics of 15-HETE mediating phosphorylation of ERK1/2 and caldesmon in rat pulmonary arterial smooth muscle cells (PASMCs). Our data showed that 15-HETE upregulated ERK1/2 phosphorylation in a dose-dependent manner, which could be blocked by ERK pathway inhibitors U0126 and PD98059. ERK1/2 phosphorylation was attenuated by inhibiting endogenous 15-HETE formation with lipoxygenase inhibitor, cinnamyl 3,4-dihydroxy-[alpha]-cyanocinnamate (CDC), in both normoxic and hypoxic PASMCs. ERK1/2 phosphorylation in response to 15-HETE was detected in cytosol as well as in nucleus and phosphorylatd ERK1/2 partly translocated into nucleus, which could be blocked by PD98059. In addition, caldesmon was phosphorylated in 15-HETE-stimulated cells; this could be inhibited by PD98059. These data demonstrated that 15-HETE is associated with ERK1/2 activation and caldesmon phosphorylation in PASMCs and that 15-HETE is at least partly involved in mediating activation of hypoxia-initiated ERK pathway, possibly leading to hypoxic pulmonary vasoconstriction.

• Authors: Changlian Lu, Ye Liu, Xiaobo Tang, Hong Ye, Daling Zhu
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 84 Issue 10 Pg. 1061-9 (Oct 2006) ISSN: 0008-4212 [Print] Canada
• PMID: 17218971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin-Binding Proteins
• Enzyme Inhibitors
• Flavonoids
• Hydroxyeicosatetraenoic Acids
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Blotting, Western
• Calmodulin-Binding Proteins (metabolism)
• Cell Nucleus (enzymology, metabolism)
• Cytosol (enzymology, metabolism)
• Enzyme Inhibitors (pharmacology)
• Flavonoids (pharmacology)
• Hydroxyeicosatetraenoic Acids (physiology)
• Hypoxia (metabolism)
• Immunohistochemistry
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Muscle, Smooth, Vascular (cytology, enzymology, metabolism)
• Phosphorylation
• Pulmonary Artery (cytology, enzymology, metabolism)
• Rats
• Rats, Sprague-Dawley
• Stimulation, Chemical
• Subcellular Fractions (enzymology, metabolism)