2023 Fiscal Year Final Research Report
Sodium-bicarbonate cotransporter NBCe1 affects hypertension and diabetes via sodium reabsorption.
| Project/Area Number |
21K08566
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柴田 茂 帝京大学, 医学部, 教授 (60508068)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 生理学 / 高血圧 / ナトリウム輸送 |
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| Outline of Final Research Achievements |
We identified the missense mutation R881S in NBCe1 variant A from the database. Immunofluorescence analysis with confocal microscopy revealed that the R881S variant was present only in the cytoplasm in both HEK293 cells and MDCK cells. Biotinylated western blotting in HEK293 cells confirmed that the cell-surface expression was completely abolished in R881S mutant. In total cell lysates, R881S-NBCe1 showed a lower molecular weight compared with wild-type, and deglycosylation study confirmed that R881S substitution impaired N-glycosylation. Electrophysiological study revealed that R881S-NBCe1 function was completely abolished.
R881S mutation inactivates the NBCe1 function without lack of dominant-negative effect. These data illustrate the diverse physiological consequences of distinct SNVs and underscore the importance of functional characterization in membrane transport proteins.
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| Free Research Field |
腎臓内科
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| Academic Significance and Societal Importance of the Research Achievements |
腎臓のナトリウム輸送の破綻は高血圧や高血圧に伴う臓器障害（脳卒中・心筋梗塞）といった重篤な疾患を引き起こすため、制圧が喫緊の課題である。
腎臓の不適切なナトリウム再吸収を行う主要な輸送体であるNBCe1の機能部位を特定し、同部位に作用する薬剤を創薬することによって、高血圧に関わる疾病の制圧に寄与することができると考える。
またNBCe1は腎臓以外にも多様な臓器に発現し、機能低下変異体の患者は片頭痛・成長障害・角膜変性などの多彩な症状を呈する。原因につながる普遍的な機能部位R881Sを同定することで、腎臓にとどまらない各疾病の解明にもつながると考える。
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