the role of p53 gene in maintenance of circadian rhythm

p53基因在维持昼夜节律中的作用

• 批准号: 23790838
• 负责人: HOSOYA Yumiko
• 金额: $ 2.66万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790838/
• 关键词: 体内時計; 老化; 遺伝子; 医療福祉

Previous studies have shown that the incidence of cardiovascular events is closely associated with circadian rhythm. It is recently reported that p53 is one of the important factors modulating the development of cardiovascular disease. However, it remains unknown whether p53 affects circadian rhythm. We examined the role of p53 gene in circadian rhythm by analyzing p53 knockout mice.Daily oscillations of behavior were analyzed with actogram. P53 knockout mice demonstrated insufficient response to the light pulse and couldn't catch up the clock-resetting. Mouse embryonic fibroblast isolated from p53 knockout mice also showed the defect of p53 attenuated the oscillations of Per2 gene. Besides, microarray analysis supported the requirement of p53 gene to keep circadian rhythm intact. From these results, it is suggested that p53 can affect circadian rhythm through some feedback pathway via Per genes and may lead to modulate the incidence of vascular events.

既往研究表明，心血管事件的发生与昼夜节律密切相关。近年来研究发现，p53是调节心血管疾病发生发展的重要因素之一。然而，p53是否影响昼夜节律仍不清楚。我们通过分析p53基因敲除小鼠，研究了p53基因在昼夜节律中的作用。P53基因敲除小鼠表现出对光脉冲的反应不足，无法赶上时钟重置。从p53基因敲除小鼠中分离的小鼠胚胎成纤维细胞也显示p53的缺陷减弱了Per2基因的振荡。此外，微阵列分析支持p53基因维持昼夜节律完整的要求。提示p53基因可能通过Per基因的某些反馈途径影响昼夜节律，从而调节血管事件的发生。

项目成果

p5 gene can modulate the incidence of vascular events through its effect on circadian rhythm

p5基因可以通过影响昼夜节律来调节血管事件的发生率