ArticleFree radical biology & medicine2017
Nitric oxide-regulated proteolysis of human CYP2B6 via the ubiquitin-proteasome system.
Article in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Unravelling Voriconazole's Hepatic Metabolism: A Narrative Review on Factors Impacting Voriconazole-N-Oxide Exposure.Mycoses · 2026Review
- Role of arachidonic acid metabolism in intervertebral disc degeneration: identification of potential biomarkers and therapeutic targets via multi-omics analysis and artificial intelligence strategies.Lipids in health and disease · 2023Article
- Nitric oxide favours tumour-promoting inflammation through mitochondria-dependent and -independent actions on macrophages.Redox biology · 2022Article
- Crosstalk between nitric oxide and retinoic acid pathways is essential for amphioxus pharynx development.eLife · 2021Article
- Therapeutic Drug Monitoring of Second- and Third-Generation Antipsychotic Drugs-Influence of Smoking Behavior and Inflammation on Pharmacokinetics.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Anti-inflammatory activity ofExperimental and therapeutic medicine · 2021Article
- Regulation of cytochrome P450 enzyme activity and expression by nitric oxide in the context of inflammatory disease.Drug metabolism reviews · 2020Review
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Tyrosine Nitration Contributes to Nitric Oxide-Stimulated Degradation of CYP2B6.Molecular pharmacology · 2020Article
- Nitric Oxide Mediated Degradation of CYP2A6 via the Ubiquitin-Proteasome Pathway in Human Hepatoma Cells.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.Acta pharmaceutica Sinica. B · 2020Review
- The relationships between cytochromes P450 and HJournal of inorganic biochemistry · 2018Review
- Posttranslational regulation of CYP2J2 by nitric oxide.Free radical biology & medicine · 2018Article
- Nitric oxide stimulates cellular degradation of human CYP51A1, the highly conserved lanosterol 14α-demethylase.The Biochemical journal · 2017Article
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3 authors at 1 institution in 1 country.
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Abstract
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated. Treatment of the cells with the NO donor (Z)-1-[N-(3-aminopropyl)-N-(3-ammoniopropyl)amino]diazen-1-ium-1,2-diolate also resulted in rapid down-regulation of CYP2B6 activity, measured as the formation of 7-hydroxy-4-trifluoromethylcoumarin, as well as 2B6 protein in the CYP2B6 HeLa cell line. CYP2B6V5 was also down-regulated by NO donors in HuH7 cells. Down-regulation was observed in the presence of cycloheximide, demonstrating that this occurs via a post-translational mechanism. We generated a HeLa cell line expressing both CYP2B6V5 and human nitric oxide synthase 2 (NOS2), the latter under positive control by tetracycline. The cellular NO produced by doxycycline treatment also effectively down-regulated CYP2B6 protein, which was blocked by the co-treatment with the NOS2 competitive inhibitor L-N
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