| Project/Area Number |
18K06646
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マンガン / 変異 / 亜鉛輸送体 / 輸送 / ZIP8 / SNP / 金属 / 毒性 |
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| Outline of Final Research Achievements |
By using immortalized cells derived from the S1, S2, and S3 regions of mouse proximal tubule, we examined Mn transport using trans-well and found that uptake from the apical side of S3 cells was high. We found that the S3 region of the proximal tubule showed high expression of ZIP8, and the reabsorption of Mn via ZIP8 from the apical side of the S3 region may regulate Mn in vivo.
We analyzed the effect of ZIP8 mutations on Mn transport in patients with congenital Hypomanganeseemia by generating DT40 cells stably expressing wild-type hZIP8 and a single mutation of four amino acids of ZIP8. The uptake rate of Mn was as low as that in ΔZIP8 cells. These results suggest that the 335 and 340 mutations in hZIP8 are located in the trans membrane domain5 and play an important role in the transport of Mn.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、ZIP8の変異と疾患との関係が報告され、Mn輸送体としてZIP8が必須であることが明らかになった。ZIP8は胆汁中あるいは腎臓の原尿中に排泄されたMnを一部回収するシステムに寄与し、全身のMn恒常性維持に重要な役割を果たしている可能性が提唱されている。しかし、ZIP8変異によるMn代謝異常症発症のメカニズムはまだ詳細には明らかになっていない。この機構を解明することは、生体で必須である金属であるMnの恒常性の調節機構の解明へと繋がる。
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