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

Guo, Lei; Tang, Xiaobo; Chu, Xiaojie; Sun, Lihua; Zhang, Lei; Qiu, Zhaoping; Chen, Shuo; Li, Yumei; Zheng, Xiaodong; Zhu, Daling

doi:10.1016/j.plefa.2008.11.007

« Previous Next »Prostaglandins, Leukotrienes and Essential Fatty Acids
Volume 80, Issue 2 , Pages 115-123, February 2009

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

Lei Guo
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Xiaobo Tang
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Xiaojie Chu
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Lihua Sun
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Lei Zhang
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Zhaoping Qiu
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Shuo Chen
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Yumei Li
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Xiaodong Zheng
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
Daling Zhu
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China
- Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, PR China
- Corresponding author at: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, PR China. Tel.: +8645186614075; fax: +8645186614073.

Received 15 July 2008; received in revised form 15 November 2008; accepted 17 November 2008. published online 25 August 2009.

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 (6.8μmol/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 () 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 through the PKC signaling pathway in pulmonary arterial smooth muscle cells.