Circadian Expression of Clock Genes in Human Oral Mucosa and Skin

Bjarnason, Georg A.; Jordan, Richard C.; Wood, Patricia A.; Li, Qi; Lincoln, David W.; Sothern, Robert B.; Hrushesky, William J. M.; Ben‐David, Yaacov

doi:10.1016/s0002-9440(10)64135-1

Cited by 352 publications

(272 citation statements)

References 52 publications

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“…These data suggest that it may be possible for the cell-cycle rhythm to be entrained to 24-h fluctuations in temperature in a rhythmic host environment. Discussion DNA synthesis, mitosis, and the expression of cell-cycle proteins in mammalian tissues (e.g., skin, bone marrow, gut, tongue, and oral mucosa) occur with a 24-h cycle in vivo (3)(4)(5)(49)(50)(51)(52)(53)(54)(55) and circadian periodicity of cell mitosis persists in rodents in constant darkness (2,5). Daily rhythms of cell-cycle protein expression (Cyclins E, A, and B1) were also observed in human oral epithelium sampled by biopsy at 4-h intervals for 24 h from healthy human subjects (3).…”

Section: Resultsmentioning

confidence: 99%

Circadian-independent cell mitosis in immortalized fibroblasts

Yeom

Pendergast

Ohmiya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperaturecompensated such that the period of the rhythm remains constant (∼24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-fourhour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.O rganization of physiology and behavior into specific time domains is a fundamental property of nearly all living organisms. Anticipation of periodic changes in the environment presumably increased survival and reinforced the development of endogenous circadian oscillators (1). Because cell division is critical to the survival of unicellular organisms and the integrity of DNA is susceptible to UV irradiation, the progression of the cell cycle was probably also strongly affected by daily changes in the environment. Indeed, multiple studies have measured diurnal fluctuations in cell division such that mitosis occurs at a specific time of day in numerous species ranging from unicellular organisms (2) to humans (3-5). These data suggest that the circadian and cell cycles may be coupled in vivo.Circadian rhythms are self-sustained oscillations in physiology and behavior with endogenous periods of ≈24 h that can be synchronized, or entrained, to environmental cues such as the light/dark cycle or temperature (6). In mammals, the master circadian clock is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Genes that are important for circadian timekeeping are expressed not only in the SCN but also in many peripheral tissues, including fibroblasts (7-11). Immortalized embryonic fibroblasts exhibit circadian rhythms of gene expression (12) and, using singlecell imaging...

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Section: Resultsmentioning

confidence: 99%

Circadian-independent cell mitosis in immortalized fibroblasts

Yeom

Pendergast

Ohmiya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…14,21,22 Parallel, human studies confined to less invasive measurements in peripheral blood, oral mucosa and skin showed similar temporal clock genes expression. [26][27][28] When Pearson's correlation coefficients between the three clock genes studied were calculated in subcutaneous AT, all genes were significant and positively correlated to each other. It is known that the CLOCK:BMAL1 heterodimer activates the transcription of period and cryptocrome genes, and it is only when PER and CRY proteins reach a critical concentration that they attenuate the CLOCK:BMAL1 transactivation, thereby generating a circadian oscillation in their own transcription.…”

Section: Discussionmentioning

confidence: 99%

Clock genes are implicated in the human metabolic syndrome

et al. 2007

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Background: Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT. Objective: We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features. Methods: Visceral and subcutaneous AT samples were obtained from morbid obese men (n ¼ 8), age: 42713 years and body mass indexX40 kg/m 2 , undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR. Results: Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (Po0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (Po0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (Po0.01). Conclusion: We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.

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“…These rhythms have also been uncovered in human bone marrow, skin, and oral and rectal mucosae (Smaaland et al 1991(Smaaland et al , 2002Bjarnason et al 2001;Bjarnason and Jordan 2002). The above 24-hour changes were first documented in laboratory rodents on light/dark (LD) synchronization and in humans on normal diurnal routine.…”

Section: Circadian Gating Of Cell Divisionmentioning

confidence: 98%