2007 Fiscal Year Final Research Report Summary
Mechanism on Hsp70-induced stabilization of ion channel and its application to the treatment for atrial fibrillation
| Project/Area Number |
18590775
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tottori University |
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Principal Investigator |
HISATOME Ichiro Tottori University, Graduate School of Medical Science, Professor (60211504)
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Haruaki Tottori University, Faculty of Medicine, Professor (80212124)
HOSHIKAWA Yoshiko Tottori University, Graduate School of Medical Science, Assistant Professor (10181489)
MIAKE Junichiro Tottori University, Faculty of Medicine, Assistant Professor (40372677)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Hsp70 / Kv1.5 / stabilization / geranyl geranyl acetone / atrial fibrillation |
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| Research Abstract |
We tested the effects of Hsp70 on the stability of Kv1.5 K^+ channel proteins using biochemical and electrophysiological techniques. Hsp70 and HSF-1 increased Kv1.5 proteins to be expressed in HeLa and COS7 cells, whereas either Hsp40, 27 or 90 did not. Hsp70 prolonged the half-life time of Kv1.5 without an increase of its ubiquitinated form, and increased the immunoreactivity of Kv1.5 in the endoplasmic reticulum and Golgi apparatus. Hsp70 also increased the amplitude of the ultrarapid delayed-rectifier K^+ current (Ik_ur) of transfected cells, which was abolished by pretreatment with brefeldin A or colchicine. Pretreatment with a Hsp70 inducer, geranyl-geranyl acetone (GGA), significantly increased Kv1.5 protein expression in COS7 cells. Pretreatment with GGA also significantly increased Ik_ur which is also abolished by brefeldin A or colchicine. In conclusion, Hsp70 stabilized the functional Kv1.5 protein.
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[Book] 不整脈 20072007
Author(s)
加藤 克, 他
Total Pages
215(79-85)
Publisher
メディカルレビュー社
Description
「研究成果報告書概要(和文)」より
