\u03b2-Arrestin 1 (ARRB1) serves as a molecular marker of the peripheral circadian rhythm

Tatsunosuke Tomita,Taisuke Mori,Yoshiaki Onishi

doi:10.1038/s41368-019-0065-y

Tatsunosuke Tomita, Taisuke Mori + Show 1 more

Open Access

https://doi.org/10.1038/s41368-019-0065-y

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Abstract

The control of the circadian rhythm is important for health because it regulates physiological functions and is associated with health hazards. We aimed to identify a circadian biomarker of health status in human saliva, since collecting saliva is non-invasive, straightforward, and cost-effective. Among 500 genes potentially controlled by the salivary clock identified using chromatin immunoprecipitation (ChIP) assays, 22 of them showed reasonable transcriptional responses according to a DNA array in a salivary model system. Among these 22 genes, ARRB1, which is expressed in human salivary glands, was also expressed in model HSG cells at the transcriptional and translational levels. The profile of ARRB1 expression in human saliva was circadian, suggesting that ARRB1 could serve as a candidate circadian biomarker in saliva. We compared ARRB1 with other biomarkers in salivary samples from jet-lagged individuals. The circadian profile of ARRB1 reflected the time lag more than the profile of melatonin, whereas the profiles of cortisol and α-amylase did not reflect the time lag. Overall, these findings suggest that salivary ARRB1 could serve as a candidate biomarker that could be used to monitor the internal body clock.

Highlights

The circadian rhythm is a biological process involving oscillation profiles that are ~ 24 h long and influence various physiological phenomena
Human internal rhythms tend to be more disrupted in fast-paced, modern, urbanized global societies. The remedy of such pathologies associated with rhythm disorders or the confirmation of their effects require the internal rhythms of individuals to be monitored
We previously reported that NR1D1 (REV-ERBα) is expressed with a circadian oscillation and was shown to be involved in the circadian Identification of clock-controlled genes in salivary cells by chromatin immunoprecipitation (ChIP)-ontranscription of the BMAL1 gene in a human submandibular chip analysis gland (HSG) cell line

Summary

Human Salivary gland

Bioluminescence/104 manner by sympathetic nerve activation by the SCN and biological and peripheral clocks. Transcripts from HSG and HeLa cells stimulated with 100 nmol·L–1 dexamethasone and human salivary gland tissues were analyzed by RT-PCR nuclear receptors RORα and REV-ERBα are important for the maintenance of circadian clock function. We previously reported that NR1D1 (REV-ERBα) is expressed with a circadian oscillation and was shown to be involved in the circadian Identification of clock-controlled genes in salivary cells by ChIP-ontranscription of the BMAL1 gene in a human submandibular chip analysis gland (HSG) cell line. Clock-controlled genes in HSG cells much is expressed in NIH 3T3 cells, which serve as a standard were initially selected by ChIP-on-chip assays of the core model of the circadian system These results indicate that both BMAL1 and REV-ERBα play important roles in circadian-based oscillator components BMAL1 and REV-ERBα. We combined the ChIP-on-chip and microarray results and selected 22 candidate genes that

RESULTS

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