Stabilizing effects of eicosapentaenoic acid on Kv1.5 channel protein expressed in mammalian cells

被引：12

作者：

Koshida, Shunya ^{[2
]}

Kurata, Yasutaka ^{[1
]}

Notsu, Tomomi ^{[2
]}

Hirota, Yutaka ^{[2
]}

Kuang, Ting Y. ^{[2
]}

Li, Peili ^{[2
]}

Bahrudin, Udin ^{[2
]}

Harada, Shingo ^{[2
]}

Miake, Junichiro ^{[3
]}

Yamamoto, Yasutaka ^{[2
]}

Hoshikawa, Yoshiko ^{[2
]}

Igawa, Osamu ^{[3
]}

Higaki, Katsumi ^{[4
]}

Soma, Masaaki ^{[5
]}

Yoshida, Akio ^{[2
]}

Ninomiya, Haruaki ^{[6
]}

Shiota, Goshi ^{[7
]}

Shirayoshi, Yasuaki ^{[2
]}

Hisatome, Ichiro ^{[2
]}

机构：

[1] Kanazawa Med Univ, Dept Physiol, Uchinada, Ishikawa 9200293, Japan

[2] Tottori Univ, Grad Sch Med Sci, Dept Genet Med & Regenerat Therapeut, Inst Regenerat Med & Biofunct,Div Regenerat Med &, Yonago, Tottori 683, Japan

[3] Tottori Univ, Fac Med, Dept Cardiovasc Med, Yonago, Tottori 683, Japan

[4] Tottori Univ, Fac Med, Dept Human Genome Sci, Yonago, Tottori 683, Japan

[5] Mochida Pharmaceut Co Ltd, Tokyo 1608515, Japan

[6] Tottori Univ, Fac Med, Dept Regulat Biol, Yonago, Tottori 683, Japan

[7] Tottori Univ, Div Mol & Genet Med, Dept Genet Med & Regenerat Therapeut, Grad Sch Med Sci, Yonago, Tottori 683, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2009年 / 604卷 / 1-3期

关键词：

EPA; DHA; Kv1.5; Ultra-rapid delayed-rectifier K+ channel current; POLYUNSATURATED FATTY-ACIDS; K+ CHANNEL; ATRIAL-FIBRILLATION; MODULATION; PREVENTION; CURRENTS; KINASE; FAMILY;

D O I：

10.1016/j.ejphar.2008.12.016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the stability of Kv1.5 channel protein. The expression and function of Kv1.5 (Kv1.5-FLAG) in transfected African green monkey kidney fibroblast cells as well as rat atrium were estimated by immunoblotting, immunoprecipitation, immunofluorescence and patch-clamp techniques. Both EPA and DHA immediately blocked Kv1.5 channel current in a dose-dependent manner, accompanied by reduction of their phosphorylation. Chronic treatment (for 12 h) with EPA at lower concentrations (0.3-10 mu M) increased the level of Kv1.5-FLAG protein as well as Kv1.5 channel current without changes in its gating kinetics, prolonging its half-life; in contrast, both EPA and DHA at higher concentrations (30-100 mu M) decreased the expression of Kv1.5-FLAG. EPA at the higher concentrations also decreased mRNA of Kv1.5 and synapse-associated protein 97 expression. EPA at the lower concentrations increased Kv1.5 expression in the endoplasmic reticulum, Golgi apparatus and cell membrane. EPA-induced increase of Kv1.5 channel expression and current was abolished by pretreatment with the protein transport inhibitor brefeldin A or colchicines, and by the Kv1.5 channel blocker 4-aminopyridine. Oral administration of EPA (30 mg/kg) increased the level of endogenous Kv1.5 in rat atria. These results indicate that chronic treatment with EPA at lower concentrations stabilizes Kv1.5 channel protein in the endoplasmic reticulum and Golgi apparatus thereby enhancing the Kv1.5 channel current on the cell membrane. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：93 / 102

页数：10

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