Role of protein kinase C in 15-HETE-induced hypoxic pulmonary vasoconstriction.
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.
Guo
Lei
L
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China.
Tang
Xiaobo
X
Chu
Xiaojie
X
Sun
Lihua
L
Zhang
Lei
L
Qiu
Zhaoping
Z
Chen
Shuo
S
Li
Yumei
Y
Zheng
Xiaodong
X
Zhu
Daling
D
D000818:Animals; D000873:Anthracenes; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism; D051670:Shaw Potassium Channels / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000873:Anthracenes; D002227:Carbazoles; D006893:Hydroxyeicosatetraenoic Acids; C496991:Kcnb1 protein, rat; C492014:Kcnc4 protein, rat; D051666:Kv1.5 Potassium Channel; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D051669:Shab Potassium Channels; D051670:Shaw Potassium Channels; C057416:KT 5720; D010569:Perylene; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C004965:hypericin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate