| Project/Area Number |
17590191
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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 |
General physiology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NIISATO Naomi Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Associate Professor, 医学研究科, 准教授 (00237645)
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| Co-Investigator(Kenkyū-buntansha) |
MARUNAKA Yoshinori Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Professor, 医学研究科, 教授 (00127036)
MIYAZAKI Hiroaki Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Research Associate, 医学研究科, 助教 (30360027)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | tyrosine dephophorylation / [Cl^-]_c / src kinase / ENaC / PTP / hypotonic stress / Na^+ reabsorption / cytosolic Cl^- / 浸透圧 / センサー / Src family kinase / クロライド / Na^+ 再吸収 |
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| Research Abstract |
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 indicated that chronic extracellular hypotonicity stimulates Na^+ reabsorption through alpha-ENaC mRNA expression in renal epithelial A6 cell. However, the osmosensing mechanism and the stimulatory mechanism of Na^+ reabsorption through ENaC gene expression are not well understood. We have recently indicated that : 1) the hypotonic stress causes a biphasic reduction of cytosolic Cl^- concentration ([Cl^-]_c), and 2) the hypotonic stress modulates tyrosine phosphorylation of src kinase playing a crucial role in signal transduction. Based on these observations, we hypothesized that cytosolic CL^-acts as a signal molecule to regulate src kinase activity in hypotonic stress and that src kinase plays a crucial role for stimulation of Na^+ reabsorption through ENaC gene expression in renal epithelia. To clarify if the cytosolic Cl^-acts as a signal molecule for the hypotonic stress, we studied the effects of ([Cl^-]_c on phosphorylation of src kinase at Tyr416 which is autophosphorylated for enzymatic activation. In the present study, we found that : 1) both activities of PTP and src kinase decrease at lowered ([Cl^-]_c, and 2) the activity of src kinase is larger than that PTP at lowered ([Cl^-]_c. Furthermore, we study if src kinase activation through reduction of ([Cl^-]_c is involved in stimulation of Na^+ reabsorption by chronic hypotonic stress. Pretreatment with PP2 (a src kinase inhibitor) significantly inhibited chronic hypotonicity-stimulated Na^+ reabsorption through suppression of ENaC mRNA expression. Based on these results, we suggest that hypotonic stress stimulates Na^+ reabsorption through induction of ENaC mRNA expression via src kinase activation by a reduction of ([Cl^-]_c in renal epithelial A6 cells.
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