Mechanism on Hsp70-induced stabilization of ion channel and its application to the treatment for atrial fibrillation

Hsp70诱导离子通道稳定的机制及其在房颤治疗中的应用

• 批准号: 18590775
• 负责人: HISATOME Ichiro
• 金额: $ 2.53万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590775/
• 关键词: Hsp70; Kv1.5; stabilization; geranyl geranyl acetone; atrial fibrillation; ゴルジ体; 細胞内輸送; CHIP

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.

我们使用生化和电生理技术测试了HSP70对KV1.5 K^+通道蛋白稳定性的影响。 HSP70和HSF-1增加了在HELA和COS7细胞中表达的KV1.5蛋白，而HSP40、27或90则没有。 HSP70延长了KV1.5的半衰期时间，而没有增加其泛素形式，并增加了内质网和高尔基体中KV1.5的免疫反应性。 HSP70还增加了转染细胞的超脂质延迟直流电k^+电流（IK_UR）的幅度，该电池通过用Brefeldin A或秋水仙碱进行了预处理而废除。用Hsp70诱导剂香烷基 - 凝萝丙酮（GGA）预处理，在COS7细胞中显着增加了KV1.5蛋白表达。用GGA进行预处理也大大增加了IK_UR，这也被Brefeldin A或Colchicine废除了。总之，HSP70稳定了功能性KV1.5蛋白。

项目成果

Effects of Pacemaker Currents on Creation and Modulation of Human Ventricular Pacemaker : a theoretical study with application to biological pacemaker engineering.

起搏器电流对人体心室起搏器产生和调节的影响：应用于生物起搏器工程的理论研究。

• 发表时间: 2006
• 期刊: Am J Physiol Heart Circ Physiol. Sep 22(Equb ahead of print)
• 作者: Ogura K;et. al.;Sonoyma K;Mizue E;Kurata Y.
• 通讯作者: Kurata Y.

Inhibition of β-Adrenergic signaling by intracellular AMP is independ ent of cell-surface adenosine receptors in rat cardiac cells.

细胞内 AMP 对 β-肾上腺素信号传导的抑制与大鼠心肌细胞中的细胞表面腺苷受体无关。

• 发表时间: 2007
• 期刊: Journal of Molecular and Cellular Cardiology 43(5)
• 作者: Ogura K;et. al.
• 通讯作者: et. al.

Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering

• DOI: 10.1152/ajpheart.00426.2006
• 发表时间: 2007-01-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Kurata, Yasutaka;Matsuda, Hiroyuki;Shibamoto, Toshishige
• 通讯作者: Shibamoto, Toshishige

Expression of oxidative stress-related molecules in circulating leukocytes and urine in patients with chronic viral hepatitis.

慢性病毒性肝炎患者循环白细胞和尿液中氧化应激相关分子的表达。

• 发表时间: 2006
• 期刊: Liver Int. 26
• 作者: Ogura K;et. al.;Sonoyma K;Mizue E;Kurata Y.;Saeki T
• 通讯作者: Saeki T

Stabilizing effects of Hsp90 on BERG channel protein

Hsp90 对 BERG 通道蛋白的稳定作用

• 发表时间: 2007
• 作者: Iwai;C.;et. al.
• 通讯作者: et. al.