| Project/Area Number |
17K15500
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Research Collaborator |
Tamai Ikumi
Nakanishi Takeo
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ABCG2 / 高尿酸血症 / 酸化ストレス / 細胞内局在 / ABCG2/BCRP / 翻訳後修飾 / 血管障害 / 内在化 / 尿酸 |
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| Outline of Final Research Achievements |
Since hyperuricemia is considered to be one of the risk factors for cardiovascular disease, this study examined the effect of uric acid on the regulation mechanism of uric acid concentration in vascular endothelial cells. It was found that the treatment with uric acid at hyperuricemia caused internalization of ABCG2, and the decrease in the expression at the plasma membrane reduced the extracellular excretion of uric acid and resulted in cell damage. In addition, it was suggested that decreased expression of Mate1 and Oct2 alters the pharmacokinetics of the substrate compound in the kidney of hyperuricemia model rats.
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| Academic Significance and Societal Importance of the Research Achievements |
高尿酸血症はメタボリックシンドロームをはじめ，様々な慢性炎症性疾患と併発することで病態の悪循環を引き起こすと考えられている．本検討で尿酸により内在化することが示されたABCG2は尿酸以外にも慢性腎臓病時に増加する尿毒症物質などの生理化合物や抗がん剤等の薬物を基質とすることから，高尿酸血症時のABCG2の内在化が他の病態進展や薬物動態変動に寄与している可能性が考えられる．
今後，ABCG2におけるどのような翻訳後修飾が局在を変化させるかを明らかにし，その修飾を調節する薬物を見出すことで，高尿酸血症に併発する疾患の増悪を抑制に繋がると期待される．
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