Transcriptional architecture of the mammalian circadian clock

Nature Reviews Genetics, Journal Year: 2016, Volume and Issue: 18(3), P. 164 - 179

Published: Dec. 19, 2016

Language: Английский

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Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

Molecules, Journal Year: 2015, Volume and Issue: 20(10), P. 18886 - 18906

Published: Oct. 16, 2015

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It present in almost all or organisms. Its synthetic pathway depends on the species which it measured. For example, tryptophan to melatonin differs plants and animals. speculated that machinery eukaryotes was inherited from bacteria as result of endosymbiosis. However, melatonin's mechanisms microorganisms are currently unknown. metabolism highly complex these enzymatic processes having evolved cytochrome C. In addition its degradation, metabolized via pseudoenzymatic free radical interactive processes. The metabolic products overlap often difficult determine process dominant. under oxidative stress, may be featured over others. Because complexity degradative processes, expected additional novel metabolites will identified future investigations. original primary function early life forms such unicellular organisms scavenger antioxidant. During evolution, selected signaling transduce environmental photoperiodic information into an endocrine message multicellular for other purposes well. As antioxidant, exhibits several unique features differ classic antioxidants. These include cascade reaction radicals capacity induced moderate stress. make potent endogenously-occurring antioxidant protects catastrophic

Language: Английский

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The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids

Endocrine Reviews, Journal Year: 2016, Volume and Issue: 38(1), P. 3 - 45

Published: Oct. 17, 2016

Abstract Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion is normally characterized by a prominent robust circadian (around 24 hours) oscillation, with daily peak around the time habitual sleep-wake transition minimal levels in evening early part night. It has long been recognized that this 24-hour rhythm partly reflects activity master pacemaker located suprachiasmatic nucleus hypothalamus. In past decade, secondary clocks based on same molecular machinery as central were found other brain areas well most peripheral tissues, adrenal glands. Evidence rapidly accumulating to indicate misalignment between host adverse effects. circulating glucocorticoid internal synchronizer system. present review examines scientific foundation these novel advances their implications for health disease prevention treatment.

Language: Английский

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Mistimed sleep disrupts circadian regulation of the human transcriptome

Proceedings of the National Academy of Sciences, Journal Year: 2014, Volume and Issue: 111(6)

Published: Jan. 21, 2014

Significance Disruption of the timing sleep–wake cycle and circadian rhythms, such as occurs during jet lag shift work, leads to disordered physiological but what extent molecular elements rhythm generation are affected is not known. Here, we show that delaying sleep by 4 h for 3 consecutive days a sixfold reduction transcripts in human blood transcriptome just 1%, whereas, at same time, centrally driven melatonin affected. Genes processes included those core gene expression. The data have implications understanding negative health outcomes disruption cycle.

Language: Английский

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Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology

Human Reproduction Update, Journal Year: 2013, Volume and Issue: 20(2), P. 293 - 307

Published: Oct. 16, 2013

Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on peripheral reproductive organs. Likewise, numerous investigations documented that stable circadian rhythms are also helpful in maintaining health. The relationship of and rhythmicity maternal fetal health is summarized this review. Databases were searched for related published English literature up 15 May 2013. search terms used various combinations included melatonin, rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress free radicals. results studies uncovered herein. Both impact reproduction, especially during pregnancy. Melatonin a multifaceted molecule with direct radical scavenging indirect antioxidant activities. produced both ovary placenta where it protects against molecular mutilation cellular dysfunction arising from oxidative/nitrosative stress. particular, often site excessive generation due less than optimal adhesion uterine wall, which leads either persistent hypoxia or intermittent reoxygenation, processes cause massive organ dysfunction. This may contribute pre-eclampsia other disorders complicate ameliorated damage fetus experiments using non-human mammals. maintenance regular light/dark sleep/wake cycle important stabilize generated by central pacemaker, nuclei. Optimal mother since her directly indirectly via rhythm, programs developing master oscillator fetus. Experimental disturbed referred as perturbed cycles negative consequences maturing oscillators, lead psychological behavioral problems newborn. To optimize prevent disturbances shift work bright light exposure at night should be avoided, trimester Finally, synergizes oxytocin promote delivery Since blood levels normally highest dark period, propensity childbirth occur relate high time concert enhance strength contractions. A number conclusions naturally evolve data review: (i) pineal placental origin, essential functions maturation placenta/uterine homeostasis; (ii) clock genes, components all cells including those organs, roles organismal (fetal maternal) physiology; (iii) potent coupled its virtual absence toxicity, indoleamine utility treatment ischemia/reperfusion, etc. (iv) parturition synergism between nocturnal increase oxytocin.

Language: Английский

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Melatonin feedback on clock genes: a theory involving the proteasome

Journal of Pineal Research, Journal Year: 2014, Volume and Issue: 58(1), P. 1 - 11

Published: Nov. 4, 2014

Abstract The expression of ‘clock’ genes occurs in all tissues, but especially the suprachiasmatic nuclei ( SCN ) hypothalamus, groups neurons brain that regulate circadian rhythms. Melatonin is secreted by pineal gland a manner as influenced . There also considerable evidence melatonin, turn, acts on directly influencing mechanisms. most direct route which melatonin could reach would be via cerebrospinal fluid third ventricle. pars tuberalis PT pituitary, another melatonin‐sensitive tissue, this route. major include period genes, Per1 and Per2 , cryptochrome Cry1 Cry2 clock (circadian locomotor output cycles kaput) gene, Bmal1 (aryl hydrocarbon receptor nuclear translocator‐like) gene. Clock heterodimers act E‐box components promoters Per Cry to stimulate transcription. A negative feedback loop between proteins nucleus allows their own cycle ubiquitination deubiquitination controls levels CRY protein degraded proteasome and, hence, amount available for feedback. Thus, it provides post‐translational component mechanism. BMAL 1 stimulates transcription REV ‐ ERB α partially regulated In ‘black widow’ model transcription, proteasomes destroy factors are needed only particular time. proposed herein, interaction required adjust changes environmental photoperiod. particular, we predict inhibition interferes with loops / PER both tend stabilize itself particularly at night when naturally elevated. account effects rhythms associated molecular timing genes. hypothalamus explaining dramatic ‘time day’ effect injections reproductive status seasonal breeders. Finally, predicts inhibitor such bortezomib modify similar melatonin.

Language: Английский

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Melatonin in type 2 diabetes mellitus and obesity

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 15(2), P. 105 - 125

Published: Dec. 7, 2018

Language: Английский

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Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

Molecular and Cellular Endocrinology, Journal Year: 2015, Volume and Issue: 418, P. 74 - 88

Published: Feb. 7, 2015

Language: Английский

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Thyroid Hormone and Seasonal Rhythmicity

Frontiers in Endocrinology, Journal Year: 2014, Volume and Issue: 5

Published: Jan. 1, 2014

Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation and migration. At temperate latitudes, changes photoperiod maintain the alignment annual rhythms with predictable environment. The appropriate physiological response to changing mammals requires retinal detection light pineal secretion melatonin, but extraretinal occurs birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone conversion. Here we review evidence circadian clock within pars tuberalis adenohypophysis links decoding local signalling medio-basal hypothalamus through conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond photoperiodic control its conversion, might be involved longer term timing processes seasonal programs. Finally, examine potential implication kisspeptin RFRP3, two RF-amide peptides expressed hypothalamus, rhythmicity.

Language: Английский

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Evidence for the Benefits of Melatonin in Cardiovascular Disease

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 20, 2022

The pineal gland is a neuroendocrine which produces melatonin, hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity neuroprotective properties. Numerous studies have that melatonin significant functions cardiovascular disease, may anti-aging ability of decrease primary hypertension needs be more extensively evaluated. benefits reducing cardiac pathology, preventing death muscle response ischemia-reperfusion rodent species. Moreover, also prevent hypertrophy heart under some circumstances, turn would lessen development failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent acts effective suppressing damage mediated by pharmacologic drugs. Therefore, cardioprotective multiple animal human studies. Herein, we summarize most established system focus on molecular mechanisms action.

Language: Английский

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