Identification of new Na^<+->driven cation transporter and its functional and pathophysiological analyses

新型Na^<->驱动的阳离子转运蛋白的鉴定及其功能和病理生理学分析

• 批准号: 16590213
• 负责人: IWAMOTO Takahiro
• 金额: $ 2.24万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590213/
• 关键词: Na^+; Ca^<2+> exchanger; Cation transporter; Expression system; Transgenic mice; Tissue distribution; イオントランスポーター; 薬理学; 生理学

Abnormal intracellular Na^+ metabolism is related to several diseases, such as hypertension, arteriosclerosis, ischemic injury, renal failure, and diabetes. Recently, we found that the role of vascular Na^+/Ca^<2+> exchanger in the pathogenesis of salt-dependent hypertension using specific exchange inhibitors and genetically engineered mice. In this study, we searched a new Na^<+->driven cation transporter, which may be involved in Na^+-dependent diseases, and identified the new transporter by gene analyses using specific motif sequences (α-repeat) of Na^+/Ca^<2+> exchanger superfamily. The identified gene was partially homologous to K^+-dependent Na^+/Ca^<2+> exchanger (NCKX). This new NCKX was abundantly expressed in heart, smooth muscle, and skeletal muscle. When this new NCKX cDNA was expressed in mammalian cells, we could detect Na^+-dependent Ca^<2+> transport activity. We are currently preparing genetically engineered mice for this new NCKX. In near future, we would like to examine the functional and pathophysiological importance of this new Nat^+-driven cation transporter using genetically engineered mice.

异常的细胞内Na^+代谢与多种疾病有关，例如高血压，动脉硬化，缺血性损伤，肾衰竭和糖尿病。最近，我们发现使用特定的交换抑制剂和基因工程小鼠，血管Na^+/Ca^<2+>交换器在盐依赖性高血压的发病机理中的作用。在这项研究中，我们搜索了一种新的Na^<+ - >驱动的阳离子转运蛋白，该转运蛋白可能与Na^+ - 依赖性疾病有关，并使用Na^+/ca^<2+> ifferanger superfamily的Na^+/ca^<2+> fiffermily的特定基序序列（α-repeat）通过基因分析鉴定了新的转运蛋白。鉴定的基因与K^+ - 依赖性Na^+/Ca^<2+>交换器（NCKX）部分同源。这种新的NCKX在心脏，平滑肌和骨骼肌中具有绝对的表现力。当这种新的NCKX cDNA在哺乳动物细胞中表达时，我们可以检测到Na^+ - 依赖性Ca^<2+>转运活性。我们目前正在为这种新的NCKX准备基因工程的小鼠。在不久的将来，我们想检查使用基因工程小鼠这种新的Nat^+驱动阳离子转运蛋白的功能和病理生理重要性。

项目成果

Endotheline-1 enhances the activity of Na^+/Ca^<2+> exchanger type 1 in renal epithelial cells.

Endotheline-1增强肾上皮细胞中1型Na 2 /Ca 2 交换器的活性。

• 发表时间: 2004
• 期刊: J.Cardiovasc.Pharmacol. 44・S1
• 作者: Kita;S.
• 通讯作者: S.

Down-regulation of Na^+/Ca^<2+> exchanger by fluvastatin in rat cardiomyoblast H9c2 cells : Involvement of RhoB in Na^+/Ca^<2+> exchanger mRNA stability.

氟伐他汀对大鼠成肌细胞H9c2细胞中Na 2 /Ca 2 交换蛋白的下调：RhoB参与Na 2 /Ca 2 交换蛋白mRNA稳定性。

• 发表时间: 2005
• 期刊: Molecular Pharmacology 68(2)
• 作者: Maeda;S.;Matsuoka;I.;Iwamoto;T.;Kurose;H.;Kimura;J.
• 通讯作者: J.

Different cation sensitivities and binding site domains of Na^+-Ca^<2+->K^+ and Na^+-Ca^<2+> exchangers.

Na^ -Ca^<2 ->K^ 和Na^ -Ca^<2> 交换剂的不同阳离子敏感性和结合位点域。

• 发表时间: 2005
• 期刊: J.Cell Physiol. 203(2)
• 作者: Uehara;A.
• 通讯作者: A.

Endothelin-1 aggravates hypoxia/reoxygenation-induced injury in renal epithelial cells through the activation of Na^+/Ca^<2+> exchanger.

内皮素-1通过激活Na 2 /Ca 2 交换剂加重肾上皮细胞缺氧/复氧诱导的损伤。

• 发表时间: 2004
• 期刊: J.Cardiovasc.Pharmacol. 44(Suppl 1)
• 作者: Iwamoto;T.
• 通讯作者: T.

Na^+/Ca^<2+>交換体(NCXl)と食塩感受性高血圧

Na^+/Ca^<2+>交换器(NCXl)和盐敏感性高血压

• 发表时间: 2006
• 期刊: 日本臨床 64・1
• 作者: Wang Y;Yoshioka K;Azam MA;Kimura T;Kuwaki T. Takuwa Y.;岩本隆宏
• 通讯作者: 岩本隆宏