The role of hypoxia and the circadian rhythm in sleep apnoea

Jaspers, Tessa; Morrell, Mary J.; Simonds, Anita K.; Adcock, Ian M.; Durham, Andrew

doi:10.1183/13993003.congress-2015.oa298

Cited by 7 publications

(7 citation statements)

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“…The presented data also indicate that alteration of the MAX transcriptional network may contribute to circadian dysfunctions observed in several pathological contexts. For instance, the downregulation of MNT has been recently proposed as a important functional event for the hypoxia response in a wide variety of injury and disease settings [51], and severe consequences caused by acute hypoxia have been correlated with defects in circadian rhythms [52][53][54]. Although diverse proteins, such as HIF1A and mTOR, appear to interfere with the clock transcriptional regulation in low oxygen conditions [55,56], our data suggest that perturbation of MAX/MNT complexes might provide an essential contribution to hypoxia-induced chronodisruption.…”

Section: Discussionmentioning

confidence: 99%

MYC-Associated Factor MAX is a Regulator of the Circadian Clock

Blaževitš

Bolshette

Vecchio

et al. 2020

IJMS

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The circadian transcriptional network is based on a competition between transcriptional activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that the MYC-associated factor X, MAX, plays a repressive role in this network and operates through a MYC-independent binding to E-box-containing regulatory regions within the promoters of circadian BMAL1 targets. We further show that this “clock” function of MAX is required for maintaining a proper circadian rhythm and that MAX and BMAL1 contribute to two temporally alternating transcriptional complexes on clock-regulated promoters. We also identified MAX network transcriptional repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. Collectively, our data indicate that MAX regulates clock gene expression and contributes to keeping the balance between positive and negative elements of the molecular clock machinery.

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Section: Discussionmentioning

confidence: 99%

MYC-Associated Factor MAX is a Regulator of the Circadian Clock

Blaževitš

Bolshette

Vecchio

et al. 2020

IJMS

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“…The presented data also indicate that alteration of MAX transcriptional network may contribute to circadian dysfunctions observed in several pathological contexts. For instance, downregulation of MNT has been recently proposed as a functional important event for the hypoxia response in a wide variety of injury and disease settings (Yang and Hurlin, 2017), and severe consequences caused by acute hypoxia have been correlated with defects in circadian rhythms (Jaspers et al, 2015; Mortola, 2007; Yu et al, 2015). Although diverse proteins, such as HIF1A and mTOR, appear to interfere with the clock transcriptional regulation in low oxygen conditions (Walton et al, 2018; Wu et al, 2017), our data suggest that perturbation of MAX/MNT complexes might provide an essential contribution to hypoxia-induced chronodisruption.…”

Section: Discussionmentioning

confidence: 99%

MYC-associated factor MAX is an essential regulator of the clock core network

Blaževitš

Bolshette

Vecchio

et al. 2019

Preprint

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The circadian transcriptional network is based on a competition between transcriptional activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that the MYC-Associated factor X, MAX, plays a repressive role in this network and operates through its MYC-independent binding to E-box-containing regulatory regions within the promoters of circadian BMAL1 targets. This clock function of MAX is essential for maintaining a proper circadian rhythm but separated by the role of MAX as a partner of MYC in controlling cell proliferation. We also identified MAX Network Transcriptional repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. Collectively, our data indicate that MAX is an integral part of the core molecular clock and keeps the balance between positive and negative elements of the molecular clock machinery. Accordingly, alteration of MAX transcriptional complexes may contribute to circadian dysfunction in pathological contexts.

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“…Differentially expressed genes in this network included cytokine receptors CXCR1 and CXCR2 , as well as the transcription factors HIF1A and LITAF . While HIF1A is known for its role in activating hypoxic response genes, recent work suggests that HIF1A induction from hypoxia caused by obstructive sleep apnea may disrupt circadian rhythms [ 48 ]. Overall stress response networks and cytokines may eventually contribute to a larger biomarker panel for diagnosing TSD, but by themselves such genes may be too variable or too pleiotropic to discriminate between sleep loss and other phenotypes such as illness.…”

Section: Discussionmentioning

confidence: 99%

Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation

et al. 2018

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BackgroundAlthough sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day.ResultsAltogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators.ConclusionsThis study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4664-3) contains supplementary material, which is available to authorized users.

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The role of hypoxia and the circadian rhythm in sleep apnoea

Cited by 7 publications

References 0 publications

MYC-Associated Factor MAX is a Regulator of the Circadian Clock

MYC-Associated Factor MAX is a Regulator of the Circadian Clock

MYC-associated factor MAX is an essential regulator of the clock core network

Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation

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