Abstract
The aim of the present study was to investigate the roles of protein kinase C (PKC) signal transduction pathway in the 15-hydroxyeicosatetraenoic acid (15-HETE)-induced down-regulation expression of K(V) 1.5, K(V) 2.1 and K(V) 3.4, and pulmonary vasoconstriction under hypoxia. Tension measurements on rat pulmonary artery (PA) rings, Western blots, semi-quantitative PCR and whole-cell patch-clamp technique were employed to investigate the effects of 15-HETE on PKC and K(V) channels. Hypericin (6.8 micromol/L), a PKC inhibitor, significantly attenuated the constriction of PA rings to 15-HETE under hypoxia. The down-regulation of K(V) 1.5, K(V) 2.1 and K(V) 3.4 channel expression and inhibition of whole-cell K currents (I(K)(V)) induced by 15-HETE were rescued and restored, respectively, by hypericin. These studies indicate that the PKC signal transduction pathway is involved in 15-HETE-induced rat pulmonary vasoconstriction under hypoxia. 15-HETE suppresses the expression of K(V) 1.5, K(V) 2.1 and K(V) 3.4 channels and inhibits I(K)(V) through the PKC signaling pathway in pulmonary arterial smooth muscle cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anthracenes
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Carbazoles / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Down-Regulation / genetics
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Gene Expression / drug effects
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Gene Expression / genetics
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Hydroxyeicosatetraenoic Acids / pharmacology*
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Hypoxia / metabolism*
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In Vitro Techniques
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Kv1.5 Potassium Channel / genetics
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Kv1.5 Potassium Channel / metabolism
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Male
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Membrane Potentials / physiology
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Muscle, Smooth, Vascular / cytology
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / metabolism
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Patch-Clamp Techniques
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Perylene / analogs & derivatives
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Perylene / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Pulmonary Artery / drug effects
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Pulmonary Artery / physiology*
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Pyrroles / pharmacology
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Rats
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Rats, Wistar
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Shab Potassium Channels / genetics
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Shab Potassium Channels / metabolism
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Shaw Potassium Channels / genetics
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Shaw Potassium Channels / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Vasoconstriction / drug effects
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Vasoconstriction / physiology*
Substances
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Anthracenes
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Carbazoles
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Hydroxyeicosatetraenoic Acids
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Kcnb1 protein, rat
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Kcnc4 protein, rat
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Kv1.5 Potassium Channel
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Protein Kinase Inhibitors
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Pyrroles
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Shab Potassium Channels
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Shaw Potassium Channels
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KT 5720
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Perylene
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15-hydroxy-5,8,11,13-eicosatetraenoic acid
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hypericin
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Tetradecanoylphorbol Acetate