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

被引：15
作者：
Guo, Lei [1 ]
Tang, Xiaobo [1 ]
Chu, Xiaojie [1 ]
Sun, Lihua [1 ]
Zhang, Lei [1 ]
Qiu, Zhaoping [1 ]
Chen, Shuo [1 ]
Li, Yumei [1 ]
Zheng, Xiaodong [1 ]
Zhu, Daling [1 ,2 ]
机构：
[1] Harbin Med Univ, Coll Pharm, Dept Biopharmaceut Sci, Harbin 150081, Heilongjiang, Peoples R China
[2] Biopharmaceut Key Lab Heilongjiang Prov, Harbin 150081, Peoples R China
来源：
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS | 2009年 / 80卷 / 2-3期
基金：
中国国家自然科学基金;
关键词：
15-Hydroxyeicosatetraenoic acid; Protein kinase A; Protein kinase C; Voltage-gated potassium channels; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE; K+ CURRENTS; CHANNEL; ARTERY; ACTIVATION; MYOCYTES; ISOFORMS; EXPRESSION;
D O I：
10.1016/j.plefa.2008.11.007
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu mol/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-KV) 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-KV through the PKC signaling pathway in pulmonary arterial smooth muscle cells. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：115 / 123
页数：9
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