Project/Area Number |
26670590
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
General surgery
|
Research Institution | University of the Ryukyus |
Principal Investigator |
NOGUCHI Hirofumi 琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 免疫抑制剤 / 副作用 / 糖尿病 / 膵島移植 / 細胞毒性 / RCAN蛋白 / 蛋白導入法 / カルシニューリンインヒビター |
Outline of Final Research Achievements |
Calcineurin inhibitors have been used for the transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects such as diabetes. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells). This peptide (11R-VIVIT) did not affect insulin secretion. However, our recent study showed that 11R-VIVIT affected cell viability when used higher concentration because of VIVIT sequence. The aim of this study is to develop another safer NFAT inhibitor (RCAN-11R) without cell viability less toxic than calcineurin inhibitors. The peptide could interfere selectively with calcineurin-NFAT interaction without affecting calcineurin phosphatase activity similar to 11R-VIVIT. RCAN-11R did not affected cell viability when used as same concentration as toxic concentration of 11R-VIVIT. Therefore, RCAN-11R could be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.
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