| Project/Area Number |
17K08673
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Nihon University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 膵β細胞障害 / 小胞体ストレス / 時計遺伝子 / Chrono遺伝子 / インスリン分泌 / 低酸素 |
|---|
| Outline of Final Research Achievements |
We here found novel function of the cicadian clock gene, CHRONO, in regulation of ER stress. The expression of CHRONO was studied in MIN6 cells and isolated mouse islets treated with the ER stress inducers thapsigargin by quantitative real-time PCR analysis. The mRNA levels of CHRONO were increased significantly in MIN6 treated with thapsiagrgin and in isolated islets treated with tunicamycin. Sequence analysis of the CHRONO locus disclosed a potential C/EBP-ATF composite element site intron 1. CHRONO expression was found to be upregulated by ER stress. However, in MEF cells lacking ATF4, ER stress failed to upregulate CHRONO expression. We are now searching glucose metabolism of CHRONO knockout mice. More research is needed to clarify the roles of CHRONO in regulation of ER stress.
|
| Academic Significance and Societal Importance of the Research Achievements |
インスリン分泌不全においても時計遺伝子が関連している事が、報告されている。サーカディアンリズムを制御する時計遺伝子は、十数個同定されているが、小胞体ストレスとの関連性を示す報告はほとんどない。Chrono遺伝子は、コア時計遺伝子を抑制する機能を有する。Chrono遺伝子が、ストレス下において、時計遺伝子の発現を調整している可能性がある。本研究の発展により、ストレス下での時計遺伝子の発現経路の新たなメカニズムの解明につながると考えられる。
|
