Role of protein kinase C in 15-HETE-induced hypoxic pulmonary vasoconstriction.

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.

• Authors: Lei Guo, Xiaobo Tang, Xiaojie Chu, Lihua Sun, Lei Zhang, Zhaoping Qiu, Shuo Chen, Yumei Li, Xiaodong Zheng, Daling Zhu
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) 2009 Feb-Mar Vol. 80 Issue 2-3 Pg. 115-23 ISSN: 0952-3278 [Print] Scotland
• PMID: 19186045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Carbazoles
• Hydroxyeicosatetraenoic Acids
• Kcnb1 protein, rat
• Kcnc4 protein, rat
• Kv1.5 Potassium Channel
• Protein Kinase Inhibitors
• Pyrroles
• Shab Potassium Channels
• Shaw Potassium Channels
• KT 5720
• Perylene
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• hypericin
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Anthracenes
• Carbazoles (pharmacology)
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Down-Regulation (genetics)
• Gene Expression (drug effects, genetics)
• Hydroxyeicosatetraenoic Acids (pharmacology)
• Hypoxia (metabolism)
• In Vitro Techniques
• Kv1.5 Potassium Channel (genetics, metabolism)
• Male
• Membrane Potentials (physiology)
• Muscle, Smooth, Vascular (cytology)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Patch-Clamp Techniques
• Perylene (analogs & derivatives, pharmacology)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Pulmonary Artery (drug effects, physiology)
• Pyrroles (pharmacology)
• Rats
• Rats, Wistar
• Shab Potassium Channels (genetics, metabolism)
• Shaw Potassium Channels (genetics, metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Vasoconstriction (drug effects, physiology)