Identifivatina and functional analysis of urate binding proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02641
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kanazawa University
• Principal Investigator: Tamai Ikumi 金沢大学, 薬学系, 教授 (20155237)
• Co-Investigator(Kenkyū-buntansha): 荒川 大 金沢大学, 薬学系, 准教授 (40709028) ; 若山 友彦 熊本大学, 大学院生命科学研究部(医), 教授 (70305100)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 尿酸 / 血清尿酸値 / CD38 / 炎症 / 免疫反応 / トランスポーター / 尿酸結合タンパク質 / 痛風

Outline of Final Research Achievements

To clarify why humans maintain high serum uric acid (SUA) levels and why SUA fluctuations are associated with pathological and physiological functions, this study hypothesized the completely new concept that there are urate-binding proteins in humans and they mediate urate associated physiological function and pathology. As a result, several urate-binding proteins were found and CD38, which was found as one of urate binding proteins, was further analyzed. It was found that crystallized uric acid increases CD38 expression in inflammatory cells, and that soluble uric acid inhibits NAD+-degrading enzyme activity of CD38. The maintenance of SUA has significance in modulating the activity of CD38. This is the first study which identified the presence of urate binding proteins and should be useful for further understanding of the roles of urate and the mechanisms for urate associated diseases in future.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

ヒトと高等霊長類でのみ特異的に高い血清尿酸値SUAの意義とSUA変動と相関する多様な病態との関連性を明確にすべく、尿酸結合タンパク質が尿酸センサーとして働いていると仮定し、複数の尿酸結合タンパク質を見出した。その一つCD38については、結晶化尿酸と可溶性尿酸がCD38のNAD+分解酵素活性を調各々正負に相異なる方向に調節することをin vitroならびにCD38欠損マウス等のin vivo試験により示した。本成果は初めて尿酸が直接作用する生体タンパク質を同定するとともに、見出したNAD+は炎症・免疫・寿命など基本的な生理機能に関連しており、今後の尿酸研究に全く新しい情報となる。