Ask about this productRelated genes to: CYP2E1 antibody
- Gene:
- CYP2E1 NIH gene
- Name:
- cytochrome P450 family 2 subfamily E member 1
- Previous symbol:
- CYP2E
- Synonyms:
- -
- Chromosome:
- 10q26.3
- Locus Type:
- gene with protein product
- Date approved:
- 1988-03-03
- Date modifiied:
- 2015-12-09
Related products to: CYP2E1 antibody
Related articles to: CYP2E1 antibody
- The ketogenic diet is increasingly used for metabolic and neurologic indications, yet its impact on hepatic mitochondrial function and xenobiotic metabolism remains incompletely defined. Cytochrome P450 2E1 (CYP2E1) is induced by the ketone body acetone and contributes to oxidative and carbonyl stress, but prior studies examining CYP2E1 regulation during ketosis have yielded conflicting results. Here, we investigated the effects of an 8-week medium chain triglyceride ketogenic diet (MCT-KD) on liver mitochondrial respiratory chain activity and CYP2E1 expression in young and aged Fisher 344 × Brown Norway F1 rats. In young animals, MCT-KD significantly reduced mitochondrial complex I activity without significant changes in complexes II, III, or IV. These changes occurred without altered citrate synthase activity, suggesting comparable mitochondrial content. In parallel, MCT-KD robustly increased hepatic CYP2E1 protein levels and activity in young and aged animals and upregulated its electron donor, P450 oxidoreductase (POR), particularly in young rats. Despite robust induction of the acetone-CYP2E1 pathway, methylglyoxal-derived protein adducts did not accumulate, even though hepatic GLO1 expression was reduced. Together, these findings demonstrate that long-term MCT-KD induces coordinated adaptations in hepatic mitochondrial function and the CYP2E1-POR pathway without increasing methylglyoxal-derived protein damage. - Source: PubMed
Publication date: 2026/08/19
Ryan Abigail SRoberts Reagan MStayer Kristina MTomasevich Alexandra AMisare Kelly RHollis FionaMcQuail Joseph AHartman Jessica H - Cancer cachexia is frequently associated with altered pharmacokinetics and increased chemotherapy toxicity due to the downregulation of cytochrome P450 (CYP) enzymes. However, the molecular mechanisms driving this broad metabolic suppression remain poorly understood. This study investigated whether tumor-derived parathyroid hormone-related protein (PTHrP) is associated with, and may contribute to, suppression of multiple CYP families. In a rat cachexia model, protein expression of CYP3A, CYP1A, CYP2C, CYP2D, and CYP2E1 was significantly downregulated in both the liver and small intestine. Consistent with these changes, pharmacokinetic analyses using a CYP substrate cocktail demonstrated markedly increased AUC and reduced clearance for probe drugs. In vitro experiments showed that PTHrP treatment reduced these CYP isoforms in primary rat hepatocytes. In human data sets, analysis of The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data set revealed a significant negative correlation between PTHrP and CYP gene expression, together with enrichment of NF-κB-related transcriptional programs. Furthermore, multimodal analysis using single-cell RNA sequencing and spatial transcriptomics demonstrated that PTHrP-high tumor regions exhibit suppressed xenobiotic metabolism. Additionally, in breast cancer liver metastases, high tumor PTHrP expression correlated with reduced CYP expression in surrounding nontumor hepatocytes, consistent with a possible paracrine relationship. Collectively, these results support an association between tumor-derived PTHrP and suppression of drug-metabolizing programs. They further suggest that PTHrP may be one contributing factor, but not definitive proof of a principal suppressor, and should therefore be considered a candidate biomarker requiring further mechanistic and clinical validation. - Source: PubMed
Publication date: 2026/06/22
Fujita IsseiKaji TsubasaNoguchi IsamuTokumaru KaiMaeda HitoshiMaruyama ToruWatanabe Hiroshi - Bisphenol S (BPS) has increasingly replaced bisphenol A, yet the molecular mechanisms underlying its low-dose hazards on male fertility remain incompletely characterized. This study systematically investigates BPS-induced reproductive toxicity by exposing male BALB/c mice to environmentally relevant doses (0, 10, 100, and 1000 μg/kg/day) for 14 or 35 days, utilizing an integrated phenotypic-to-multi-omics workflow. Notably, phenotypic and functional impairments exhibited a distinct time-dependent pattern; while 14-day exposure induced no significant alterations, prolonged (35-day) BPS exposure at 100 μg/kg impaired overall sperm motility, reduced mean angular displacement (MAD), and induced testicular germ cell apoptosis without causing measurable systemic toxicity, revealing a selective gonadotoxic phenotype. Mechanistically, RNA sequencing of testicular tissue and untargeted metabolomic profiling of epididymal sperm uncovered a coordinated "gene-pathway-metabolite-phenotype" regulatory axis. BPS transcriptionally suppressed steroidogenic pathway components, an effect corroborated by a dose-dependent decline in intratesticular testosterone (T) across all treatment groups and a compensatory elevation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), with LH showing greater sensitivity at the lowest dose. Sperm metabolomics further identified a statistically specific downregulation of prostaglandin F2α (PGF2α) dimethyl amine within the arachidonic acid metabolism network, with all adjacent prostaglandin branches remaining unaltered. This perturbation was cross-validated by the congruent dysregulation of upstream phase-I and phase-II biotransformation transcripts, Cyp2e1 and Ugt1a1, identified as shared regulatory nodes across both omics platforms. Collectively, these findings provide mechanistic insight into how BPS impairs sperm motility via a targeted disruption of the steroidogenesis-prostaglandin signaling axis and offer cross-omics evidence supporting a re-evaluation of BPS safety margins as a bisphenol A substitute. - Source: PubMed
Publication date: 2026/08/18
Lin XiaotanLiu HuanMa WeiLu ShuoLi BoZhang WenLi NingChen Tingting - N,N-dimethylformamide is a widely used industrial solvent and a well-recognized occupational hepatotoxicant, which can induce multiple forms of hepatocyte death. However, whether necroptosis, a receptor-interacting protein kinase (RIPK)-dependent programmed necrotic cell death, is the predominant form in N,N-dimethylformamide-induced hepatotoxicity remains unclear. In this study, we identified necroptosis as a major mode of cell demise induced by N,N-dimethylformamide in AML12 hepatocytes (0-40 mM) and cytochrome P450 2E1-overexpressing HepG2 (CYP2E1-HepG2) cells (0-400 mM). N,N-dimethylformamide-induced acute liver injury in C57BL/6 mice (2.0 g/kg bw for 48 h) and AML12 hepatocyte damage (40 mM) were both significantly suppressed by two specific necroptosis inhibitors: necrostatin-1 (targeting RIPK1) and necrosulfonamide (targeting mixed lineage kinase domain-like protein, MLKL). Furthermore, conditioned culture medium from N,N-dimethylformamide-exposed hepatocytes induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in apoptosis-associated speck-like protein containing a CARD (ASC)-expressing RAW264.7 macrophages (ASC-RAW264.7), which could be blocked by necroptosis inhibitors. Collectively, these findings strongly support a model in which acute N,N-dimethylformamide exposure triggers hepatocyte necroptosis, which in turn activates the NLRP3 inflammasome in liver macrophages and exacerbates inflammatory liver injury by secreting pro-inflammatory cytokines. - Source: PubMed
Publication date: 2026/08/15
Zhang Xiu-NingChen Jing-JingWang ShuoZhang Yan-JingWang Wei-RuZeng Tao - Hypoxic pregnancy promotes fetal growth restriction (FGR) and preterm birth, for which antenatal corticosteroids (ACS) are recommended to prevent respiratory distress. Adults born FGR or preterm are at greater risk of health conditions requiring medication(s), which are metabolised by hepatic cytochrome P450 (CYP) enzymes. We determined if ACS and/or hypoxic pregnancy alters fetal and adult offspring hepatic CYP activity. Ewes carrying singletons were randomly allocated to normoxic (Nx) or hypoxic (Hx; 11% O) pregnancy from 105 to 138 dGA (term = 147 dGA). Dexamethasone (Dex, 12 mg IM) or vehicle (saline IV) was administered at 115 and 116 dGA. Ewes carrying male fetuses were humanely killed at 138 ± 2 dGA, while female fetuses lambed spontaneously and were humanely killed at 9 months (9 mo). Hepatic CYP activity was quantified using functional assays, and expression of glucocorticoid signalling and CYP regulating proteins was determined via Western blot. Hx increased fetal hepatic CYP2B6 and CYP2D6 activity, expression of 11β-HSD1&2 and reduced GRα-A nuclear expression, and cytosolic GRβ:α-A ratio. Dex reduced fetal CYP3A metabolism of testosterone to metabolites 6β-OHT and 2α-OHT, and GRα-A and GRβ cytosolic expression. Fetal CYP2B6 activity positively correlated with CAR in Nx, but not Hx. In 9 mo lambs, Hx reduced CYP2C19 activity and PPARα and GRβ cytosolic expression. Dex decreased CYP1A2, CYP2B6, CYP2E1 activity, and CYP3A testosterone metabolism to 6β-OHT. HxDex increased cytosolic and nuclear GRβ:α-A. Hx and Dex differentially effect hepatic CYP activity in offspring, and changes to CYP activity may be due to a loss of regulatory control. - Source: PubMed
Publication date: 2026/08/13
Bennett Millicent G AMeakin Ashley SBotting-Lawford Kimberley JNiu YouguoFord Sage GWiese Michael DGiussani Dino AMorrison Janna L