Regulatory mechanism of Na+ reabsorption by hypotonicity through regulatory volume decrease-dependent dephosphorylation of FAK.

通过调节 FAK 体积减少依赖性去磷酸化，通过低渗性调节 Na 重吸收的机制。

• 批准号: 15590189
• 负责人: NIISATO Naomi
• 金额: $ 2.05万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590189/
• 关键词: Tyrosine dephophorylation; [Cl^-]_c; NPPB; Regulatory volume decrease; Foacal adhesion kinase; Hypotonic shock; forcal adhesion kinase; チロシン脱リン酸化酵素; イオン輸送

Epithelial Na^+ transport in the kidney is important for control of blood pressure and extracellular fluid volume and is regulated by plasma osmolality and hormones. We have already indicated that Na^+ reabsorption is stimulated by extracellular hypotonicity in renal epithelial A6 cell that is a model cell line to study regulatory mechanism of Na^+ reabsorpption. However, the regulatory mechanism behind this is not well understood. Hypotonic shock causes the initial cell swelling followed by regulatory volume decrease(RVD) which is involved in the decrease in cytosolic Cl^- concentration ([Cl^-]_c). Our aim in this study is to clarify the hypothesis that RVD has a crucial role in hyposmotic regulation of Na^+ reabsorption in renal epithelium. We found that 1)hypotonic shock reduced [Cl^-]_c through RVD process by measuring [Cl^-]_c with Cl^- fluorescence dye (N-(6-methoyquinolyl) acetoxy-acetyl-ester, MQAE), 2)hypotonic shock caused dephosphoryaltion of foacal adhesion kinase(FAK) which was abolished by blockade of RVD by NPPB (a Cl^- channel blocker), 3)blockade of RVD caused the sustained tyrosine phosphorylation of FAK, 4)hypotonicity-induced Na^+ reabsorption and epithelial Na^+ channel gene expression were abolished by blocking RVD by NPPB. Taken together these results, it is suggested that hypotonic shock stimulated Na^+ reabsorption RVD-dependent FAK tyrosine dephosphorylation in renal epithelial A6 cells.

肾脏中的上皮Na^+转运对于控制血压和细胞外液量很重要，并受血浆渗透压和激素的调节。我们已经在研究Na^+重吸收调节机制的模型细胞系肾上皮A6细胞中指出，细胞外低渗刺激Na^+重吸收。然而，这背后的监管机制并不清楚。低渗休克引起初始细胞肿胀，随后是调节性容积减少（RVD），这与胞质Cl^-浓度（[Cl^-] c）的降低有关。本研究的目的是阐明RVD在肾上皮Na^+重吸收的低渗调节中起关键作用的假说。用Cl^-荧光染料测定[Cl ^-]_c，发现低渗休克通过RVD过程降低[Cl ^-]_c（2）低渗休克引起黏着斑激酶（foacal adhesion kinase，FAK）的去磷酸化，而NPPB阻断RVD可使FAK的去磷酸化消失（一种Cl^-通道阻断剂）; 3）阻断RVD可引起FAK的持续酪氨酸磷酸化; 4）NPPB阻断RVD可消除低渗诱导的Na^+重吸收和上皮Na^+通道基因表达。综合以上结果，我们认为低渗休克刺激了肾上皮A6细胞Na^+重吸收RVD依赖性FAK酪氨酸去磷酸化。

项目成果

Naomi Niisato, Hoyoku Nishino, Kyosuke Nishio, Yoshinori Marunaka: "Cross talk of cAMP and flavone in regulation of cyctic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells"Biochemic

Naomi Niisato、Hoyoku Nishino、Kyosuke Nishio、Yoshinori Marunaka：“cAMP 和黄酮在肾上皮 A6 细胞中循环纤维化跨膜电导调节器 (CFTR) Cl- 通道和 Na /K /2Cl- 协同转运蛋白调节中的交叉对话”Biochemic

Flavonoid-induced ENaC expression in the kidney of Dahl salt-sensitive rat.

Dahl 盐敏感大鼠肾脏中类黄酮诱导的 ENaC 表达。

• 发表时间: 2004
• 期刊: Biochem Biophys Res Commun 315
• 作者: Wataru Aoi;Naomi Niisato;Hiroaki Miyazaki;Yoshinori Marunaka
• 通讯作者: Yoshinori Marunaka

Benzamil, a blocker of epithelial Na(+) channel-induced upregulation of artery oxygen pressure level in acute lung injury rabbit ventilated with high frequency oscillation.

• DOI: 10.1016/j.bbrc.2004.12.098
• 发表时间: 2005-02
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Nobuko Taguchi;N. Niisato;Y. Sawabe;H. Miyazaki;Yasutomi Hirai;Y. Marunaka

Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells

• DOI: 10.1016/j.bcp.2003.10.026
• 发表时间: 2004-02-15
• 期刊: BIOCHEMICAL PHARMACOLOGY
• 影响因子: 5.8
• 作者: Niisato, N;Nishino, H;Marunaka, Y
• 通讯作者: Marunaka, Y

New concept of spare receptors and effectors

• DOI: 10.1007/s00232-004-0729-0
• 发表时间: 2005-01-01
• 期刊: JOURNAL OF MEMBRANE BIOLOGY
• 影响因子: 2.4
• 作者: Marunaka, Y;Niisato, N;Miyazaki, H
• 通讯作者: Miyazaki, H