Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder

Takimoto, Mieko; Hamada, Akinobu; Tomoda, Akemi; Ohdo, Shigehiro; Ohmura, Takafumi; Sakato, Hisao; Kawatani, Junko; Jodoi, Takako; Nakagawa, Hiroo; Terazono, Hideyuki; Koyanagi, Satoru; Higuchi, Shun; Kimura, Miyuki; Tukikawa, Hiroshi; Irie, Shin; Saito, Hideyuki; Miike, Teruhisa

doi:10.1152/ajpregu.00126.2005

Cited by 61 publications

(50 citation statements)

References 45 publications

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“…4a). The highest hPer1 transcription in peripheral blood was previously observed in healthy human subjects at times experienced as morning [10,11,13,14]. The current result was consistent with these previous reports.…”

Section: Levels Of Plasma Noradrenalinesupporting

confidence: 93%

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Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

Burioka

Koyanagi²,

Endo

et al. 2008

European Respiratory Journal

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Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnoea syndrome (OSAS) influences clock gene function, the present authors examined Period1 (Per1) mRNA expression in vitro and in vivo.In eight healthy subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) and Per1 mRNA expression in peripheral whole blood were measured. Expression of Per1 mRNA in cultured cells was examined under IL-6 or noradrenaline stimulation in vitro. After noradrenaline was administered to mice in vivo, Per1 mRNA expression in the brain was examined.The concentrations of serum IL-6, hsCRP and plasma noradrenaline were elevated in OSAS patients, but improved by continuous positive airway pressure (CPAP) therapy. Per1 mRNA expression in the peripheral blood significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL-6 did not directly induce Per1 mRNA in vitro. Administration of noradrenaline induced Per1 mRNA in the cerebral cortex of mice in vivo.The current study revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction, and continuous positive airway pressure helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in obstructive sleep apnoea syndrome may be one of the factors involved in disorders of Period1 mRNA expression.

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Section: Levels Of Plasma Noradrenalinesupporting

confidence: 93%

“…Although a detailed molecular mechanism of the circadian oscillator has been revealed in rodents that are nocturnally active, there have been few studies in diurnally active humans. Recently, human peripheral blood cells have been used for representative estimations of the mRNA expression of clock genes in other peripheral tissues [10][11][12][13][14].…”

mentioning

confidence: 99%

Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

Burioka

Koyanagi²,

Endo

et al. 2008

European Respiratory Journal

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“…1b-e, the mRNA expression of BMAL1, PER1, PER2 and PER3 exhibited slight but significant 24 h rhythmicity (χ 2 =12.9, p<0.01 for BMAL1; χ 2 =22.9, p<0.001 for PER1; χ 2 =22.0, p<0.001 for PER2; χ 2 =25.0, p<0.001 for PER3; Friedman test to evaluate rhythmicity). Similarly to previous reports [6][7][8]21], the levels of PER1, PER2 and PER3 peaked in the early morning and dropped to a trough level in the evening. On the other hand, the mRNA levels of CLOCK, CRY1 (Fig.…”

Section: Study 1 Because Biological Clock Function In Leucocytes Issupporting

confidence: 87%

“…Recent studies revealed that the circadian clock system consists essentially of a set of clock genes [1,2]. The circadian clock resides in the hypothalamic suprachiasmatic nucleus (SCN), which is recognised as being the master clock, and the same clock exists also in almost all peripheral tissues, including liver, heart, kidney [3][4][5] and leucocytes [6][7][8]. Although the SCN is not essential for driving peripheral oscillations, it appears to coordinate peripheral clocks [5].…”

Section: Introductionmentioning

confidence: 99%

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

et al. 2008

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Aim/hypothesis Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes. Methods Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young nondiabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 agematched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR.Results In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p<0.05) lower in patients with diabetes than in non-diabetic individuals at one or more time points. Moreover, the amplitudes of mRNA expression rhythms of PER1 and PER3 genes tended to diminish in patients with diabetes. In study 2, leucocytes obtained from patients with diabetes expressed significantly (p<0.05) lower transcript levels of BMAL1, PER1 and PER3 compared with leucocytes from control individuals, and transcript expression was inversely correlated with HbA 1c levels (ρ=−0.47 to −0.55, p<0.05). Conclusions/interpretation These results suggest that rhythmic mRNA expression of clock genes is dampened in peripheral leucocytes of patients with type 2 diabetes. The impairment of the circadian clock appears to be closely associated with the pathophysiology of type 2 diabetes in humans.

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“…Recently, human PBMCs have been used as a surrogate to estimate likely mRNA expression of clock genes in other peripheral tissues (16 -18). The greatest hPer1 transcription was observed in human subjects during the morning hours (17,18,31).…”

Section: Glucocorticoid Induces Human Period1 Mrnamentioning

confidence: 96%

Circadian Rhythms in the CNS and Peripheral Clock Disorders: Function of Clock Genes: Influence of Medication for Bronchial Asthma on Circadian Gene

et al. 2007

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Abstract. Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or β 2 -adrenoceptor agonists may influence clock genes in vivo. In our studies of clock gene mRNA expressions in human bronchial epithelial cells in vitro and peripheral blood cells in vivo, we demonstrated that glucocorticoid or β 2 -adrenoceptor agonist treatment strongly induced human Per1 mRNA expression both in vitro and in vivo. Human peripheral blood cells provide a useful indication of peripheral clock gene mRNA expression in vivo.

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Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder

Abstract: . Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder.

Cited by 61 publications

References 45 publications

Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

Circadian Rhythms in the CNS and Peripheral Clock Disorders: Function of Clock Genes: Influence of Medication for Bronchial Asthma on Circadian Gene

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