ArticleScientific reports2018
Circadian clock disruption by selective removal of endogenous carbon monoxide.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- Carbon Monoxide in an Experimental Model of Chronic Pelvic Pain Syndrome: The Effects of CORM-A1 on Pain and Anxiety-Related Behaviors.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.Medicinal research reviews · 2025Review
- Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.Cell reports · 2024Article
- The Role of Circadian Rhythms in Stroke: A Narrative Review.Neurochemical research · 2024Review
- Membrane-Bound Redox Enzyme CytochromeInternational journal of molecular sciences · 2024Article
- Circadian dependency of microglial heme oxygenase-1 expression and inflammation determine neuronal injury in hemorrhagic stroke.Journal of inflammation (London, England) · 2023Article
- Review
- A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Redox Regulatory Changes of Circadian Rhythm by the Environmental Risk Factors Traffic Noise and Air Pollution.Antioxidants & redox signaling · 2022Review
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks.Biology · 2021Review
- Ischemic Stroke and Sleep: The Linking Genetic Factors.Cardiology and therapy · 2021Review
- Review
- Carbon Monoxide: from Poison to Clinical Trials.Trends in pharmacological sciences · 2021Review
- Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.Communications biology · 2021Article
- Heme binding to human CLOCK affects interactions with the E-box.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Waterpipe smoke and e-cigarette vapor differentially affect circadian molecular clock gene expression in mouse lungs.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian rhythms are regulated by transcription-translation feedback loops (TTFL) of clock genes. Previous studies have demonstrated that core transcriptional factors, NPAS2 and CLOCK, in the TTFL can reversibly bind carbon monoxide (CO) in vitro. However, little is known about whether endogenous CO, which is continuously produced during a heme metabolic process, is involved in the circadian system. Here we show that selective removal of endogenous CO in mice considerably disrupts rhythmic expression of the clock genes. A highly selective CO scavenger, hemoCD1, which is a supramolecular complex of an iron(II)porphyrin with a per-O-methyl-β-cyclodextrin dimer, was used to remove endogenous CO in mice. Intraperitoneal administration of hemoCD1 to mice immediately reduced the amount of internal CO. The removal of CO promoted the bindings of NPAS2 and CLOCK to DNA (E-box) in the murine liver, resulting in up-regulation of the E-box-controlled clock genes (Per1, Per2, Cry1, Cry2, and Rev-erbα). Within 3 h after the administration, most hemoCD1 in mice was excreted in the urine, and heme oxygenase-1 (HO-1) was gradually induced in the liver. Increased endogenous CO production due to the overexpression of HO-1 caused dissociation of NPAS2 and CLOCK from E-box, which in turn induced down-regulation of the clock genes. The down-regulation continued over 12 h even after the internal CO level recovered to normal. The late down-regulation was ascribed to an inflammatory response caused by the endogenous CO reduction. The CO pseudo-knockdown experiments provided the clear evidence that endogenous CO contributes to regulation in the mammalian circadian clock.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.