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.

我们利用生物化学和电生理技术检测了Hsp 70对Kv1.5钾离子通道蛋白稳定性的影响。Hsp 70和HSF-1增加了HeLa和COS 7细胞中Kv1.5蛋白的表达，而Hsp 40、27或90则没有。热休克蛋白70延长了Kv1.5的半衰期，但没有增加其泛素化形式，并增加了内质网和高尔基体中Kv1.5的免疫反应性。热休克蛋白70还增加了转染细胞的超快速延迟整流钾电流（Ik_ur）的幅度，而这种作用可被布雷菲德菌素A或秋水仙碱所阻断。用Hsp 70诱导剂香叶基-香叶基丙酮（GGA）预处理COS 7细胞，显著增加Kv1.5蛋白的表达。用GGA预处理也显著增加Ik_ur，其也被布雷菲德菌素A或秋水仙素消除。总之，Hsp 70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 inward rectifier K^+ currents by angiotensin II in rat atrial myocytes : lack of effects in cells from spontaneous hypertensive rats.

血管紧张素II对大鼠心房肌细胞内向整流Kk电流的抑制：对自发性高血压大鼠的细胞缺乏作用。

• 发表时间: 2006
• 期刊: Hypertension Res. 29
• 作者: Sonoyma K;et al.
• 通讯作者: et al.

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.

Inhibition of p-Adrenergic signaling by intracellular AMP is independent of cell-surface adenosine receptors in rat cardiac cells

细胞内 AMP 对 p-肾上腺素能信号传导的抑制不依赖于大鼠心肌细胞中的细胞表面腺苷受体

• 发表时间: 2007
• 期刊: JMCC 43(5)
• 作者: Ogura;K.;et. al.
• 通讯作者: et. al.

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.