| Project/Area Number |
14207007
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
NABESHIMA Yo-ichi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60108024)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMORI Toshihiko Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80301274)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2004: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2003: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2002: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
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| Keywords | Klotho / NaK-ATPase / 1α-hydroxylase / Aging / Calcium / Vitamin D / 個体老化 / Klotho遺伝子 / カルシウムホメオスタシス / 1-α hydroxylase / グルクロニダーゼ / 1-αhydroxylase |
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| Research Abstract |
We recently developed a unique short lifespan mouse strain in which a single gene mutation caused multiple aging-related disorders and identified the responsible gene as klotho. The klotho gene is expressed principally in the important tissues for calcium homeostasis such as distal tubule cells of the kidney, choroid plexus, and theparathyroid gland. The most representative phenotypes in kl-/-mice seem to be caused by abnormalities in calcium metabolism.
To study the molecular function and the biological role of the Klotho protein, we tried to isolate Klotho binding proteins and identified Na+/K+ ATPase. Klotho is critical for the regulation of recruitment of Na+/K+ ATPase to cell surface membrane in response to the extra-cellular conditions. We next confirmed that Na+/K+ ATPase activity correlates with the amounts of Na+/K+ATPase present on the cell surface. Therefore, Klotho is involved in the regulation of Na+/K+ ATPase activity by mediating the extra-cellular signal to up or down regulation of the recruitment of Na+/K+ ATPase to cell surface.
As Na+/K+ATPase has been reported to be a fundamental regulator of multiple phenomena, Klotho can be involved in the regulation of multiple biological events by modulating the action of Na+/K+ATPase and thus deficiency of Klotho leads to multiple phenotypes.
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