Circadian clock genes oscillate in human peripheral blood mononuclear cells

Boivin, Diane B.; James, Francine O.; Wu, Aibin; Cho-Park, Park F.; Xiong, Huabao; Sun, Zhong Sheng

doi:10.1182/blood-2003-03-0779

Cited by 295 publications

(226 citation statements)

References 12 publications

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“…Per gene expression has been reported in human lymphocytes (47,48). Furthermore, human Per1 gene daily variations have been shown to have a similar acrophase and peak in both PBMCs and peripheral polymorphonuclear cells (49).…”

Section: Discussionmentioning

confidence: 97%

Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Arjona

Sarkar

2005

The Journal of Immunology

188

141

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A growing body of knowledge is revealing the critical role of circadian physiology in the development of specific pathological entities such as cancer. NK cell function participates in the immune response against infection and malignancy. We have reported previously the existence of a physiological circadian rhythm of NK cell cytolytic activity in rats, suggesting the existence of circadian mechanisms subjacent to NK cell function. At the cellular level, circadian rhythms are originated by the sustained transcriptional-translational oscillation of clock genes that form the cellular clock apparatus. Our aim in this study was to investigate the presence of molecular clock mechanisms in NK cells as well as the circadian expression of critical factors involved in NK cell function. For that purpose, we measured the circadian changes in the expression of clock genes (Per1, Per2, Bmal1, Clock), Dbp (a clock-controlled output gene), CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin), and cytokines (IFN-γ and TNF-α) in NK cells enriched from the rat spleen. The results obtained from this study demonstrate for the first time the existence of functional molecular clock mechanisms in NK cells. Moreover, the circadian expression of cytolytic factors and cytokines in NK cells reported in this study emphasizes the circadian nature of NK cell function.

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Section: Discussionmentioning

confidence: 97%

Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Arjona

Sarkar

2005

The Journal of Immunology

188

141

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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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“…The loops that drive 24 hr-rhythms, or circadian rhythms comprise the molecular clock. Importantly, the clockwork machinery is present in virtually all cell types [9] including those of the immune system [10]. The master clock of the SCN relays signals which then synchronise molecular clocks found within central and peripheral tissues [11].…”

Section: The Clockwork Machinerymentioning

confidence: 99%