Disease relevance of Cyp2e1

• In conclusion, forced overfeeding with a high-fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction [1].
• These findings indicate that metabolism is obligatory for the development of chloroform-induced hepatic, renal, and nasal toxicity and that cytochrome P450 2E1 appears to be the only enzyme responsible for this cytotoxic-related metabolic conversion under these exposure conditions [2].
• The expression of CYP 2E1 was slightly induced after single-dose and markedly induced after repeated dose-treatments of mice with hashish (10 mg kg(-1) body weight) [3].
• Microscopic alterations included bronchoalveolar adenomas, and in one Cyp2e1+/+ mouse treated with 100 mg/kg urethane, a bronchoalveolar carcinoma was diagnosed [4].
• The levels of expression of mRNA for a polycyclic aromatic hydrocarbon-inducible (CYP1A2) and an ethanol-inducible (CYP2E1) form of P-450 were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis endotoxin administration [5].

High impact information on Cyp2e1

• Liver tissues were used to measure triglyceride and fatty acid content, activity of superoxide dismutases (SOD) and glutathione peroxidase (GPx), glutathione (GSH), and cytochrome P-450 2E1 expression [6].
• Cytochrome P450 2E1, mitochondrial generation of peroxides, thiobarbituric acid reactants, and ethane exhalation were increased [7].
• Enhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: role of cytochrome P450 2E1 and 2A5 [8].
• Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice [9].
• C57BL/6 mice were injected intraperitoneally with pyrazole (Pyr) to induce CYP2E1 [9].

Chemical compound and disease context of Cyp2e1

• Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease [10].
• The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H [11].
• Disulfiram and its breakdown product diethyldithiocarbamate (DDTC) have been investigated for their potential to protect against chemically-induced toxicity and carcinogenesis because of their inhibitory effects on cytochrome P450 2E1 [12].
• Cytochrome P450 2E1-dependent aniline and p-nitrophenol hydroxylases activities in microsomal incubations were significantly inhibited by Moutan Cortex. Abrogation of toxicity was also mirrored in DNA fragmentation [13].
• These results on CYP2E1 induction demonstrate that primary mouse hepatocytes, when using ethanol and allyl alcohol as substrates and in insulin-free medium, provide a suitable system for the studies of the role of CYP2E1 in xenobiotic metabolism and toxicity [14].

Biological context of Cyp2e1

• cDNA sequence, deduced amino acid sequence, predicted gene structure and chemical regulation of mouse Cyp2e1 [15].
• Male B6C3F(1), Sv/129 wild-type (Cyp2e1+/+), and Sv/129 CYP2E1 knockout (Cyp2e1-/- or Cyp2e1-null) mice were exposed 6 h/day for 4 consecutive days to 90 ppm chloroform by inhalation [2].
• Induced pathological changes and regenerative cell proliferation were absent in these target sites in Cyp2e1-/- mice exposed to 90 ppm chloroform [2].
• Twenty hours after parenteral treatment of AKR/J (colon tumor resistant) and SWR/J (susceptible) mice with DMH.2HCl (70 mg/kg), functional levels of Cyp1a1 and Cyp2e1 were examined by measuring O-deethylation of ethoxyresorufin (EROD) and hydroxylation of p-nitrophenol, respectively [16].
• A mouse cDNA clone for the ethanol-inducible cytochrome P-450 (P450IIE1) was obtained by screening a liver cDNA library with an oligonucleotide representing a consensus sequence found in the orthologous rat, human, and rabbit sequences [17].

Anatomical context of Cyp2e1

• The activities of lauric acid 12-hydroxylation (a marker for Cyp4a) and aniline p-hydroxylation (a marker for Cyp2e1) in liver microsomes were increased 1.4- to 1.9-fold in female jvs/jvs-type mice [18].
• These observations indicated that glucocorticoid hormone plays a role in modifying expression of Cyp2e-1 and that the mouse hepatocyte culture is useful for examining its regulation mechanism [19].
• The alcohol treatment increased PNPH activities in hepatic microsomes from wild-type mice but not from Cyp2e1(-/-) mice [20].
• Ballooned hepatocytes with multiple vacuoles in their cytoplasm were observed in the livers of Cyp2e1(+/+) mice 24 and 48h after treating with CCl(4) [21].
• The bone marrow of male and female B6C3F1 mice was analyzed by Western blot analysis and immunohistochemistry to determine whether cytochrome P450 2E1 is present, and, if present, in which cell types [22].

Associations of Cyp2e1 with chemical compounds

• Parallel control and treated groups, excluding Cyp2e1-null mice, also received an i.p. injection (150 mg/kg) of the irreversible cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) twice on the day before exposures began and 1 h before every exposure [2].
• Fasting and administration of acetone and 4-methylpyrazole increased Cyp2e1 mRNA as well as protein and activity in both obese and lean mice [23].
• Cyp2e1(-/-) and Cyp1a2(-/-) mice are more resistant to acetaminophen hepatotoxicity than wild-type strains, even though the amounts of the other forms of P450s are unaltered in the liver [24].
• Mouse ethanol-inducible cytochrome P-450 (P450IIE1). Characterization of cDNA clones and testosterone induction in kidney tissue [17].
• Inhibition of cytochrome P450 2E1 expression by 2-(allylthio)pyrazine, a potential chemoprotective agent: hepatoprotective effects [25].

Co-localisations of Cyp2e1

• Using an anti-arylacetamide antiserum the primary protein adduct detected following administration of 3'-hydroxyacetanilide (300 and 600 mg/kg) to mice was a 50 kDa microsomal protein that co-migrated with cytochrome P450 2E1 [26].

Regulatory relationships of Cyp2e1

• Cyp2e1 mRNA was dramatically enhanced (12.7-fold increase) while Cyp2b10 mRNA remained unchanged and Cyp1a1 was decreased or not detected [27].
• These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform [28].

Other interactions of Cyp2e1

• Cytochrome P450 4a (Cyp4a) and Cyp2e1 are potential hepatic sources of ROS [29].
• Targeted disruption of the HNF1alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNF1alpha target genes [30].
• To test the combined roles of CYP1A2 and CYP2E1 in an intact animal model, a double-null mouse line lacking functional expression of CYP1A2 and CYP2E1 was produced by cross-breeding Cyp1a2-/- mice with Cyp2e1-/- mice [31].
• Cyp3a11 and Cyp2e1 mRNAs were not affected by any of the cytokines that were studied [32].
• The present data indicate that while Cyp2e1 is still inducible in obese mice by xenobiotics and fasting, full constitutive expression of Cyp2e1 requires leptin to be present [23].

Analytical, diagnostic and therapeutic context of Cyp2e1

• A monoclonal antibody (Mab 1-98-1) specific to rat ethanol-inducible P450 recognized a major band of Mr 51,000 in Western immunoblots of mouse liver microsomes [33].
• In situ hybridization analysis of hepatic cytochrome P450 2E1 messenger ribonucleic acid in mice. Modulation of expression by acetone [34].
• We examined 1) relative induction of Cyp2e1 protein by immunoblotting, 2) relative induction of enzyme catalytic activity (p-nitrophenol hydroxylation), and 3) Cyp2e1 mRNA levels associated with acute and chronic treatment regimens [35].
• In order to investigate the role of phosphorylation in determining murine Cyp2e-1 levels, serine 129 was changed by site-directed mutagenesis to amino acids that could not be phosphorylated and the recombinant proteins expressed in COS 7 cells [36].
• Quantification of CYP2E1-dependent hydroxylation of chlorzoxazone (CLX) by high-performance liquid chromatography (HPLC; functional analysis) was used to characterize specific enzymatic activities [37].

References