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
- Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF), with acute kidney injury (AKI) contributing substantially to morbidity and mortality in those patients. To determine whether APAP-induced AKI depends on hepatic CYP2E1-mediated bioactivation, we used CYP2E1^flox/flox^ mice treated with AAV8-TBG-Cre to selectively delete hepatic CYP2E1 while preserving renal metabolism. Male and female mice received APAP (600mg/kg) and were evaluated up to 48hours for liver and kidney injury. Liver-specific CYP2E1 deletion reduced APAP hepatotoxicity, confirming the reduction of hepatic NAPQI formation. Despite this protection, both male and female mice treated with AAV8-TBG-Cre and APAP developed progressive renal injury, with marked increases in blood urea nitrogen (BUN) and creatinine, tubular vacuolation, and strong induction of KIM-1 and osteopontin, along with cell death at 48hours. Notably, female mice lacking renal CYP2E1 and showing no detectable renal protein adducts still progressed to AKI, demonstrating that kidney injury can occur through CYP-independent mechanisms. Given that APAP-induced AKI is a delayed injury, we further considered p-aminophenol (PAP), a deacetylation product of APAP, as a potential CYP-independent contributor. These findings support the concept that non-CYP pathways, including PAP formation, may contribute to kidney injury during the later phase of toxicity, although this pathway likely represents only one component of a multifactorial injury process. Together, these results demonstrate that APAP-induced AKI is a kidney-intrinsic process that can develop independently of both hepatic and renal CYP2E1 activity, emphasizing the need for kidney-specific therapeutic strategies for preventing APAP-induced renal injury. - Source: PubMed
Publication date: 2026/08/21
Etemadi YasamanFields Timothy ARamachandran AnupJaeschke Hartmut - 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