ArticleBritish journal of pharmacology2019
Role of the CLOCK protein in liver detoxification.
Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 71 citations in OpenAlex.
- Impact of NPAS2 on mPFC dopamine synthesis and nap behavior.Nature communications · 2026Article
- Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026Review
- Impact of ViP3Aa 86 expressing transgenic maize on the health of Wistar rats: a toxicological study.Toxicology research · 2025Article
- Disruption of circadian rhythm as a potential pathogenesis of nocturia.Nature reviews. Urology · 2025Review
- Optimizing Chronotherapy in Psychiatric Care: The Impact of Circadian Rhythms on Medication Timing and Efficacy.Clocks & sleep · 2024Review
- Chronobiology of Cancers in the Liver and Gut.Cancers · 2024Review
- Chrono-tailored drug delivery systems: recent advances and future directions.Drug delivery and translational research · 2024Review
- Review
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma.Scientific reports · 2023Article
- METTL3 exacerbates insulin resistance in hepatocytes by regulating mNutrition & metabolism · 2023Article
- A review of food contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin and its toxicity associated with metabolic disorders.Current research in food science · 2023Review
- The PPARα/CYP4A14 bile acid pathway is associated with lipid metabolism disorders caused by low birth weight with high-fat diet.Food & nutrition research · 2023Article
- Molecular Oscillator Affects Susceptibility of Caterpillars to Insecticides: Studies on the Egyptian Cotton Leaf Worm-Insects · 2022Article
- L-Theanine inhibits melanoma cell growth and migration via regulating expression of the clock gene BMAL1.European journal of nutrition · 2022Article
- The molecular pathogenesis of triptolide-induced hepatotoxicity.Frontiers in pharmacology · 2022Review
- Grain-Sized Moxibustion Heightens the AntiTumor Effect of Cyclophosphamide in Hepa1-6 Bearing Mice.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- GC-MS Profile of Hua-Feng-Dan and RNA-Seq Analysis of Induced Adaptive Responses in the Liver.Frontiers in pharmacology · 2022Article
- Circadian Rhythm Effects on the Molecular Regulation of Physiological Systems.Comprehensive Physiology · 2021Review
- Early-life undernutrition induces enhancer RNA remodeling in mice liver.Epigenetics & chromatin · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeWhether and how circadian clock proteins regulate drug detoxification are not known. Here, we have assessed the effects of CLOCK (a core circadian clock protein) on drug metabolism and detoxification. EXPERIMENTAL APPROACH: Regulation by CLOCK protein of drug-metabolizing enzymes was assessed using Clock knockout (Clock KEY
resultsClock deletion disrupted hepatic diurnal expressions of a number of drug-metabolizing enzymes in mice. In particular, CYP2A4/5 expressions were markedly down-regulated, whereas CYP2B10 was up-regulated. Positive regulation of Cyp2a4/5 and negative regulation of Cyp2b10 by CLOCK were confirmed in Hepa-1c1c7 and AML-12 cells. Based on a combination of luciferase reporter, mobility shift, and ChIP assays, we found that CLOCK activated Cyp2a4/5 transcription via specific binding to E-box elements in promoter region and repressed Cyp2b10 transcription through REV-ERBα/β (two target genes of CLOCK and transcriptional repressors of Cyp2b10). Furthermore, Clock ablation sensitized mice to coumarin toxicity by down-regulating CYP2A4/5-mediated metabolism (a detoxification pathway) and to cyclophosphamide toxicity by up-regulating CYP2B10-mediated metabolism (generating the toxic metabolite 4-hydroxycyclophosphamide). CONCLUSION AND IMPLICATIONS: CLOCK protein regulates metabolism by the cytochrome P450 family and drug detoxification. The findings improve our understanding of the crosstalk between circadian clock and drug detoxification.
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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.