Functional analysis of novel ER stress related protein

2019 Fiscal Year Final Research Report

• 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: YAMAGUCHI Suguru 日本大学, 医学部, 研究医員 (70451614)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵β細胞障害 / 小胞体ストレス / 時計遺伝子

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.

Free Research Field

糖尿病

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。