Search Results (9)

Oxidative alcohol metabolism in the liver relies on sequential enzymatic reactions involving alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and aldehyde dehydrogenase (ALDH) isozymes. However, the circadian regulation of these enzymes, their susceptibility to genetic, environmental, and metabolic disruption, and their functional implications toward alcohol-mediated tissue injury remain incompletely defined. To address this gap, we performed a comprehensive integrative analysis of the publicly available circadian transcriptome datasets spanning genetic clock disruption, acute sleep deprivation, chronic high-fat diet feeding, and occupational shift work to systematically characterize the temporal regulation and disruption vulnerability of the major alcohol-metabolizing enzymes. Mouse tissue-cycling analyses revealed pronounced gene- and tissue-specific diurnal regulation, with Adh1 oscillating primarily in adipose tissues; Cyp2e1 and mitochondrial Aldh2 cycling broadly across kidney, aorta, lung, adrenal gland, and liver; and cytosolic Aldh1b1 being uniformly arrhythmic. In the liver, Cyp2e1 and Aldh2 exhibited robust ~24 h oscillations that peaked during the light/resting phase, while Adh1 showed inconsistent rhythmicity and Aldh1b1 remained arrhythmic. Notably, Cyp2e1 and Aldh2 rhythms persisted in Bmal1 knockout and Clock mutant livers under light–dark conditions, despite complete loss of core clock gene oscillations, yet were abolished in constant darkness, revealing that systemic zeitgeber cues can mask the loss of intrinsic clock function to maintain apparent rhythmicity in these metabolic genes. Systematic cross-paradigm comparison established a novel gene-specific vulnerability hierarchy. Aldh2 was found to be most disrupted by environmental and metabolic perturbations, with acute sleep deprivation eliminating its rhythmicity and temporal expression pattern and a Western-style high-fat diet inducing pronounced phase delays and rhythm loss relative to low-fat diet controls. Both disruptions paralleled alterations in hepatocyte nuclear factor 4α (Hnf4a), newly implicating HNF4α as a potential mediator of ALDH2 circadian instability. In humans, ALDH2 and CYP2E1 exhibited conserved but phase-inverted circadian rhythms across multiple tissues relative to mice, and, importantly, night-shift workers showed markedly dampened and phase-shifted ALDH2 rhythms in peripheral blood mononuclear cells, providing the molecular link between occupational circadian misalignment and impaired acetaldehyde detoxification. Collectively, our detailed and innovative analytical approach reveals gene- and tissue-specific circadian regulation of alcohol-metabolizing enzymes, identifies ALDH2 as uniquely vulnerable to circadian misalignment, underscores the importance of circadian timing for optimal hepatic detoxification and resistance to tissue injury, and suggests that monitoring circadian rhythms could help tailor individualized advice on alcohol consumption for shift workers and populations with irregular sleep schedules, informing precision medicine approaches for alcohol-related disorders. Full article

Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens). Full article

Circadian entrainment to the environmental day–night cycle is essential for the optimal use of environmental resources. In insects, opsin-based photoreception in the compound eye and ocelli and CRYPTOCHROME1 (CRY1) in circadian clock neurons are thought to be involved in sensing photic information, but the genetic regulation of circadian light entrainment in species without light-sensitive CRY1 remains unclear. To elucidate a possible CRY1-independent light transduction cascade, we analyzed light-induced gene expression through RNA-sequencing in Nasonia vitripennis. Entrained wasps were subjected to a light pulse in the subjective night to reset the circadian clock, and light-induced changes in gene expression were characterized at four different time points in wasp heads. We used co-expression, functional annotation, and transcription factor binding motif analyses to gain insight into the molecular pathways in response to acute light stimulus and to form hypotheses about the circadian light-resetting pathway. Maximal gene induction was found after 2 h of light stimulation (1432 genes), and this included the opsin gene opblue and the core clock genes cry2 and npas2. Pathway and cluster analyses revealed light activation of glutamatergic and GABA-ergic neurotransmission, including CREB and AP-1 transcription pathway signaling. This suggests that circadian photic entrainment in Nasonia may require pathways that are similar to those in mammals. We propose a model for hymenopteran circadian light-resetting that involves opsin-based photoreception, glutamatergic neurotransmission, and gene induction of cry2 and npas2 to reset the circadian clock. Full article

Circadian rhythms control almost all aspects of physiology and behavior, allowing temporal synchrony of these processes between each other, as well as with the external environment. In the immune system, daily rhythms of leukocyte functions can determine the strength of the immune response, thereby regulating the efficiency of defense mechanisms to cope with infections or tissue injury. The natural light/dark cycle is the prominent synchronizing agent perceived by the circadian clock, but this role of light is highly compromised by irregular working schedules and unintentional exposure to artificial light at night (ALAN). The primary concern is disrupted circadian control of important physiological processes, underlying potential links to adverse health effects. Here, we first discuss the immune consequences of genetic circadian disruption induced by mutation or deletion of specific clock genes. Next, we evaluate experimental research into the effects of disruptive light/dark regimes, particularly light-phase shifts, dim ALAN, and constant light on the innate immune mechanisms under steady state and acute inflammation, and in the pathogenesis of common lifestyle diseases. We suggest that a better understanding of the mechanisms by which circadian disruption influences immune status can be of importance in the search for strategies to minimize the negative consequences of chronodisruption on health. Full article

Cryptochrome (CRY) is a kind of flavin-binding protein that can sense blue light and near-ultraviolet light, and participates in the light response of organisms and the regulation of the circadian clock. The complete open reading frame (ORF) of CiPlant-CRY1 (GenBank ID OM389130.1), encoding one kind of CRY, was cloned from the Antarctic ice alga Chlamydomonas sp. ICE-L. The quantitative real-time PCR study showed that the expression level of the CiPlant-CRY1 gene was the highest at 5 °C and salinity of 32‰. CiPlant-CRY1 was positively regulated by blue or yellow light, suggesting that it is involved in the establishment of photomorphology. The CiPlant-CRY1 gene can respond to polar day and polar night, indicating its expression is regulated by circadian rhythm. The expression level of CiPlant-CRY1 was most affected by UVB irradiation, which may be related to the adaptation of ice algae to a strong ultraviolet radiation environment. Moreover, the recombinant protein of CiPlant-CRY1 was expressed by prokaryotic expression. This study may be important for exploring the light-induced rhythm regulation of Antarctic ice algae in the polar marine environment. Full article

In recent times, there has been an unprecedented increase in usage of electrical lightning. This has led to increase in artificial light at night (ALAN), and it has been suggested as a source of environmental pollution. ALAN exposure has been reported to be associated with disruption of daily rhythms and serious health consequences, such as immune, metabolic, and cognitive dysfunctions in both birds and mammals. Given the worldwide pervasiveness of ALAN, this research topic is also important from an ecological perspective. In birds, daily timings and appropriate temporal niches are important for fitness and survival. Daily rhythms in a wide array of functions are regulated by the circadian clock(s) and endogenous oscillators present in the body. There is accumulating evidence that exposure to ALAN disrupts clock-regulated daily rhythms and suppresses melatonin and sleep in birds. Circadian clock, melatonin, and sleep regulate avian cognitive performance. However, there is limited research on this topic, and most of the insights on the adverse effects of ALAN on cognitive functions are from behavioural studies. Nevertheless, these results raise an intriguing question about the molecular underpinning of the ALAN-induced negative consequences on brain functions. Further research should be focused on the molecular links between ALAN and cognitive performance, including the role of melatonin, which could shed light on the mechanism by which ALAN exposures lead to negative consequences. Full article

Light is an important environmental cue, and exposure to artificial light at night (ALAN) may disrupt organismal physiology and behavior. We investigated whether ALAN led to changes in clock-gene expression, diel activity patterns, and fecundity in laboratory populations of the mosquito Culex pipiens f. molestus (Diptera, Culicidae), a species that occurs in urban areas and is thus regularly exposed to ALAN. Populations were kept under 16 h:8h light:dark cycles or were subjected to an additional 3.5 h of light (100–300 lx) in the evenings. ALAN induced significant changes in expression in all genes studied, either alone (period) or as an interaction with time (timeless, cryptochrome2, Clock, cycle). Changes were sex-specific: period was down-regulated in both sexes, cycle was up-regulated in females, and Clock was down-regulated in males. ALAN-exposed mosquitoes were less active during the extra-light phase, but exposed females were more active later in the night. ALAN-exposed females also produced smaller and fewer eggs. Our findings indicate a sex-specific impact of ALAN on the physiology and behavior of Culex pipiens f. molestus and that changes in clock-gene expression, activity, and fecundity may be linked. Full article

Light signaling pathways interact with the circadian clock to help organisms synchronize physiological and developmental processes to periodic environmental cycles. The plant photoreceptors responsible for clock resetting have been characterized, but signaling components that link the photoreceptors to the clock remain to be identified. Members of the family of NIGHT LIGHT–INDUCIBLE AND CLOCK-REGULATED (LNK) genes play key roles linking light regulation of gene expression to the control of daily and seasonal rhythms in Arabidopsis thaliana. Particularly, LNK1 and LNK2 were shown to control circadian rhythms, photomorphogenic responses, and photoperiod-dependent flowering time. Here we analyze the role of the four members of the LNK family in Arabidopsis in these processes. We found that depletion of the closely related LNK3 and LNK4 in a lnk1;lnk2 mutant background affects circadian rhythms, but not other clock-regulated processes such as flowering time and seedling photomorphogenesis. Nevertheless, plants defective in all LNK genes (lnkQ quadruple mutants) display developmental alterations that lead to increased rosette size, biomass, and enhanced phototropic responses. Our work indicates that members of the LNK family have both distinctive and partially overlapping functions, and are an essential link to orchestrate light-regulated developmental processes. Full article

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock’s genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types. Full article