抄録
Various physiological phenomena are under the control of an endogenous circadian rhythm. The molecular circadian clock system is thought to be based on transcriptional/translational feedback loops consisting of several “clock genes” and their products. Cell cycle progression is regulated through several different cyclin dependent kinase (Cdk) regulatory mechanisms. Cdk inhibitors play important roles in cell cycle control by coordinating internal and/or external signals and impeding proliferation at several key check points. Out of several Cdk inhibitors, p21 is an important mediator of cell cycle arrest imposed by the tumor suppressor p53 in response to DNA damage. p21 gene is regulated by clock system, because its promoter has RevErb/ROR binding elements and Bmal1 gene promoter has a same regulation site. Cholic acid has reported to regulate the cell cycle through the p21 gene expression. We still do not know how clock and cholic acid regulate the p21 gene expression in the mouse liver. In mouse liver, expression of p21 mRNA exhibits weak circadian rhythm in normal food, but cholic acid containing diet causes a robust circadian rhythm. However other organs like small intestine and heart, cholic acid did not affect p21 expression. Interestingly, in the Clock mutant mice, cholic acid strongly up-regulates the p21 gene expression through the whole day.In summary, cholic acid intake under clock mutation may strongly inhibit cell division in a liver through the up-regulation of p21. [Jpn J Physiol 55 Suppl:S114 (2005)]
