Involvement of K+ channel-dependant pathways in lipoxin A4-induced protective effects on hypoxia/reoxygenation injury of cardiomyocytes

被引：17

作者：

Chen, Xiao-Qing ^{[1
]}

Wu, Sheng-Hua ^{[1
]}

Zhou, Yu ^{[1
]}

Tang, Yan-Rong ^{[1
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Pediat, Nanjing 210029, Jiangsu, Peoples R China

来源：

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS | 2013年 / 88卷 / 05期

关键词：

Lipoxin A(4); Hypoxia/reoxygenation; Potassium channel; Heme oxygenase-1; Cardiomyocytes; SENSITIVE POTASSIUM CHANNELS; HEME OXYGENASE-1; ENDOTHELIAL-CELLS; A(4); REPERFUSION; ISCHEMIA; INFLAMMATION; PROTEIN; INHIBITION; MECHANISM;

D O I：

10.1016/j.plefa.2013.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Studies have shown that lipoxin A(4) (LXA(4)) and activation of LXA(4) receptor provided protection against myocardial ischemia/reperfusion injury in animal models. However, the mechanisms by which LXA(4) induced protective role on myocardial ischemia/reperfusion injury remains unclear. In the present studies, we investigated the protective effects of LXA(4) on H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) injury and involvement of heme oxygenase-1 (HO-1)- and K+ channel-dependant pathways in the LXA(4) action. H9c2 cardiomyocytes were pretreated with or without LXA(4) or HO-1 specific interfering RNA (siRNA) or various blockers and openers of K+ channels before exposing to H/R injury. The levels of lactate dehydrogenase (LDH) and creatine kinase (CM) in cellular supernatants and necrosis factor-alpha (TNF-alpha) in cellular lysates were measured by using ELISA. Expressions of HO-1 mRNA and protein were analyzed by using RT-PCR and Western blot respectively. Pretreatment of the cells undergoing H/R injury with LXA(4) significantly reduced the LDH and CM levels induced by H/R injury, and increased the expressions and activity of HO-1. However, the protective effects of LXA4 were completely blocked by transfection of the cells with HO-1 siRNA, and were partially but significantly blocked by pretreatment of the cells with various blockers of K+ channels. The LXA(4)-induced expressions of HO-1 in the cells were also inhibited by HO-1 siRNA and various blockers of K+ channels. The inhibitory effects of LXA(4) on enhanced TNF-alpha levels induced by H/R injury were abolished by transfection of the cells with HO-1 siRNA. In conclusion, the protective role of LXA(4) on cardiomyocytes against H/R injury is related to upregulation of HO-1 via reduced production of TNF-alpha and activation of ATP-sensitive K+ channels and calcium-sensitive K+ channel. (c) 2013 Elsevier Ltd. All rights reserved.

引用

页码：391 / 397

页数：7

共 43 条

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