The molecular clock mechanism underlying the circadian rhythm of cellular metal level: interaction between molecular clock and cellular metal

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670079
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: OHDO Shigehiro 九州大学, 薬学研究科(研究院), 教授 (00223884)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 薬学 / 生体リズム / 体内時計 / 時計遺伝子 / 金属元素

Outline of Final Research Achievements

Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. In this study, we identified a 24-hr rhythm in iron levels in colon-26 tumors implanted in mice and the expression of iron regulatory protein 2 (IRP2). Furthermore, IRP2 regulated the 24-hr rhythm of transferrin receptor 1 (TfR1) mRNA expression post-transcriptionally by binding to RNA stem-loop structures known as iron-response elements. The transcription of IRP2 mRNA was promoted by circadian clock genes, including BMAL1 and CLOCK heterodimer. The expression of IRP2 in tumor cells was affected by the circadian organization of the molecular clock. Our findings suggest that circadian organization contributes to cell proliferation by regulating iron metabolism and may play a role in the circadian rhythm of other metals.

Free Research Field

時間薬理学