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Role of 15-hydroxyeicosatetraenoic acid in phosphorylation of ERK1/2 and caldesmon in pulmonary arterial smooth muscle cells.
- Source :
-
Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2006 Oct; Vol. 84 (10), pp. 1061-9. - Publication Year :
- 2006
-
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.
- Subjects :
- Animals
Blotting, Western
Cell Nucleus enzymology
Cell Nucleus metabolism
Cytosol enzymology
Cytosol metabolism
Enzyme Inhibitors pharmacology
Flavonoids pharmacology
Hypoxia metabolism
Immunohistochemistry
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular enzymology
Phosphorylation
Pulmonary Artery cytology
Pulmonary Artery enzymology
Pulmonary Artery metabolism
Rats
Rats, Sprague-Dawley
Stimulation, Chemical
Subcellular Fractions enzymology
Subcellular Fractions metabolism
Calmodulin-Binding Proteins metabolism
Hydroxyeicosatetraenoic Acids physiology
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Muscle, Smooth, Vascular metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0008-4212
- Volume :
- 84
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Canadian journal of physiology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17218971
- Full Text :
- https://doi.org/10.1139/y06-057