Intestinal Expression of Mouse Abcg2/Breast Cancer Resistance Protein (BCRP) Gene Is under Control of Circadian Clock-activating Transcription Factor-4 Pathway

Hamdan, Ahmed M.; Koyanagi, Satoru; Wada, Erika; Naoki, Katsuhiko; Murakami, Yûichi; Matsumoto, Naoya; Ohdo, Shigehiro

doi:10.1074/jbc.m111.333377

Cited by 47 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we found that the rhythmic phase of circadian gene expression in the SCN of cynomolgus monkeys was similar to that reported previously in nocturnal rodents (Kume et al, 1999;Smale et al, 2003). However, the mRNA expression of circadian clock genes and clock-controlled genes in the peripheral tissues of monkeys oscillated at opposite phases in rodents (Hoogerwerf et al, 2007;Sládek et al, 2007;Murakami et al, 2008;Hamdan et al, 2012). Previous studies comparing rhythmicity between diurnal and nocturnal species reveal that the rhythmic phase of circadian gene expression in the SCN is similar among both species (Mrosovsky et al, 2001;Caldelas et al, 2003;Lambert et al, 2005), but rhythmicity in the expression of clock genes and clock-controlled genes in the peripheral cells is largely different between nocturnal and diurnal animals (Lambert and Weaver, 2006).…”

Section: Discussionsupporting

confidence: 89%

Circadian Modulation in the Intestinal Absorption of P-Glycoprotein Substrates in Monkeys

et al. 2015

Self Cite

View full text Add to dashboard Cite

Recent studies in laboratory rodents have revealed that circadian oscillation in the physiologic functions affecting drug disposition underlies the dosing time-dependent change in pharmacokinetics. However, it is difficult to predict the circadian change in the drug pharmacokinetics in a diurnal human by using the data collected from nocturnal rodents. In this study, we used cynomolgus monkeys, diurnal active animals, to evaluate the relevance of intestinal expression of P-glycoprotein (P-gp) to the dosing time dependency of the pharmacokinetics of its substrates. The rhythmic phases of circadian gene expression in the suprachiasmatic nuclei (the mammalian circadian pacemaker) of cynomolgus monkeys were similar to those reported in nocturnal rodents. On the other hand, the expression of circadian clock genes in the intestinal epithelial cells of monkeys oscillated at opposite phases in rodents. The intestinal expression of P-gp in the small intestine of monkeys was also oscillated in a circadian time-dependent manner. Furthermore, the intestinal absorption of P-gp substrates (quinidine and etoposide) was substantially suppressed by administering the drugs at the times of day when P-gp levels were abundant. By contrast, there was no significant dosing time-dependent difference in the absorption of the non-P-gp substrate (acetaminophen). The oscillation in the intestinal expression of P-gp appears to affect the pharmacokinetics of its substrates. Identification of circadian factors affecting the drug disposition in laboratory monkeys may improve the predictive accuracy of pharmacokinetics in humans.

show abstract

Section: Discussionsupporting

confidence: 89%

Circadian Modulation in the Intestinal Absorption of P-Glycoprotein Substrates in Monkeys

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…The third group contains ATP-binding cassette transporters like multi-drug resistance-associated proteins and P-glycoprotein, which facilitate the transport of xenobiotics from outside the cell. The daily rhythms of the gene expression of ATP-binding cassette transporters were recently reported in mice and rats (24,25,33,34).…”

Section: Pharmacokineticsmentioning

confidence: 88%

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

Tahara¹,

Shibata²

2014

J Pharmacol Sci

View full text Add to dashboard Cite

Molecular mechanisms of the circadian clock systemThe circadian clock system has been widely maintained in many species, from prokaryotes to mammals. "Circadian" means "around [a] day" in Latin, and therefore "circadian rhythm" refers to a cycle of approximate 24 h. The earth rotates once every 24 h, and the circadian system has evolved to adjust functions and behavior to this cycle in order to efficiently utilize sunlight for photosynthesis in the case of plants and cyanobacteria and to obtain food in the case of animals. One of the most important features of our circadian system is that circadian clocks can endogenously maintain time under constant darkness and without external stimuli, suggesting that our body has its own internal clocks. In 1972, Moore and Eichler (1) investigated the effects of destroying the suprachiasmatic nucleus (SCN) in the rat hypothalamus. Their results revealed the loss of sleep-wake cycles and corticosterone rhythms. Since then, the SCN is regarded as the location of the master clock system in mammals. The SCN receives light-dark information directly through the retinal-hypothalamic tract and organizes the local clock in the peripheral tissues through multiple pathways involving neural and hormonal functions (2, 3). The molecular mechanism of the circadian system in mammals has been well studied over the past two decades. The transcriptional-translational feedback loop of the major clock genes Bmal1, Clock, Per1/2, and Cry1/2 is the main component of the circadian system (2) (Fig. 1A). Bmal1 and Clock, which are transcriptional activators, play a positive role in activating the Per and Cry genes through a specific promoter sequence known as the E-box. Per and Cry are translated into proteins in the cytoplasm and are then transported back into the nucleus after interacting with each other, and they subsequently stop their transcription by binding to BMAL1 and CLOCK. Thus, Per and Cry are rhythmically expressed over a 24-h period. This transcriptional regulation induces rhythmic expression of approximately 10% of all genes in each peripheral cell (4 -6). In addition to such transcriptional regulation of the circadian clock, post-transcriptional regulation and translational regulation have recently been reported to play important roles in maintaining circadian rhythms. Genome-wide RNA-seq and Chip-seq analyses found that only 22% of the rhythmically oscillating messenger RNAs are driven by de novo transcription, with RNA polymerase II recruitment and chromatin remodeling also exhibiting such rhythms (7). Furthermore, it was reported that the non-transcriptional redox cycle has a 24-h rhythm in Chrono-biology, Chrono-pharmacology, and Chrono-nutrition Tokyo 162-8480, Japan Received October 25, 2013; Accepted January 5, 2014 Abstract. The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep-wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light-dark cycle, food...

show abstract

“…This mechanism interconnects the positive and negative limbs of circadian clockwork circuitry and also regulates 24-hour variation in output physiology through the periodic activation/repression of clock-controlled output genes (30). ATF4 also acts as an output component of the circadian clock and regulates the rhythmic expression of its target genes through the CRE (31).…”

Section: Discussionmentioning

confidence: 99%

Rhythmic Control of the ARF-MDM2 Pathway by ATF4 Underlies Circadian Accumulation of p53 in Malignant Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

The sensitivity of cancer cells to chemotherapeutic agents varies according to circadian time. Most chemotherapeutic agents ultimately cause cell death through cell-intrinsic pathways as an indirect consequence of DNA damage. The p53 tumor suppressor gene (TRP53) configures the cell deaths induced by chemotherapeutic agents. In this study, we show that the transcription factor ATF4, a component of the mammalian circadian clock, functions in circadian accumulation of p53 protein in tumor cells. In murine fibroblast tumor cells, ATF4 induced the circadian expression of p19ARF (Cdkn2a). Oscillation of p19ARF interacted in a time-dependent manner with MDM2, a specific ubiquitin ligase of p53, resulting in a rhythmic prevention of its degradation by MDM2. Consequently, the half-life of p53 protein varied in a circadian timedependent manner without variation in mRNA levels. The p53 protein accumulated during those times when the p19ARF-MDM2 interaction was facilitated. Notably, the ability of the p53 degradation inhibitor nutlin-3 to kill murine fibroblast tumor cells was enhanced when the drug was administered at those times of day during which p53 had accumulated. Taken together, these results suggested that ATF4-mediated regulation of the p19ARF-MDM2 pathway underlies the circadian accumulation of p53 protein in malignant cells. Furthermore, they suggest an explanation for how the sensitivity of cancer cells to chemotherapeutic agents is enhanced at those times of day when p53 protein has accumulated, as a result of circadian processes controlled by ATF4. Cancer Res; 73(8);

show abstract

Intestinal Expression of Mouse Abcg2/Breast Cancer Resistance Protein (BCRP) Gene Is under Control of Circadian Clock-activating Transcription Factor-4 Pathway

Cited by 47 publications

References 23 publications

Circadian Modulation in the Intestinal Absorption of P-Glycoprotein Substrates in Monkeys

Circadian Modulation in the Intestinal Absorption of P-Glycoprotein Substrates in Monkeys

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

Rhythmic Control of the ARF-MDM2 Pathway by ATF4 Underlies Circadian Accumulation of p53 in Malignant Cells

Contact Info

Product

Resources

About