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Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario

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Book cover Cytochrome P450 2E1: Its Role in Disease and Drug Metabolism

Part of the book series: Subcellular Biochemistry ((SCBI,volume 67))

Abstract

Research on Cytochrome P450 2E1 (CYP2E1), a key enzyme in alcohol metabolism has been very well documented in literature. Besides the involvement of CYP2E1 in alcohol metabolism as illustrated through the studies discussed in the chapter, recent studies have thrown light on several other aspects of CYP2E1 i.e. its extrahepatic expression, its involvement in several diseases and pathophysiological conditions; and CYP2E1 mediated carcinogenesis and modulation of drug efficacy. Studies involving these interesting facets of CYP2E1 have been discussed in the chapter focusing on the recent observations or ongoing studies illustrating the crucial role of CYP2E1 in disease development and drug metabolism.

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References

  • Abdelmegeed MA, Carruthers NJ, Woodcroft KJ, Kim SK, Novak RF (2005) Acetoacetate induces CYP2E1 protein and suppresses CYP2E1 mRNA in primary cultured rat hepatocytes. J Pharmacol Exp Ther 315(1):203–213

    Article  PubMed  CAS  Google Scholar 

  • Abdelmegeed MA, Moon KH, Chen C, Gonzalez FJ, Song BJ (2010) Role of cytochrome P450 2E1 in protein nitration and ubiquitin-mediated degradation during acetaminophen toxicity. Biochem Pharmacol 79(1):57–66

    Article  PubMed  CAS  Google Scholar 

  • Abdelmegeed MA, Yoo SH, Henderson LE, Gonzalez FJ, Woodcroft KJ, Song BJ (2011) PPARalpha expression protects male mice from high fat-induced nonalcoholic fatty liver. J Nutr 141(4):603–610

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Razzak Z, Loyer P, Fautrel A, Gautier JC, Corcos L, Turlin B, Beaune P, Guillouzo A (1993) Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol 44(4):707–715

    PubMed  CAS  Google Scholar 

  • Albano E, Comoglio A, Clot P, Iannone A, Tomasi A, Ingelman-Sundberg M (1995) Activation of alkylhydrazines to free radical intermediates by ethanol-inducible cytochrome P-4502E1 (CYP2E1). Biochim Biophys Acta 1243(3):414–420

    Article  PubMed  Google Scholar 

  • Albano E, Clot P, Morimoto M, Tomasi A, Ingelman-Sundberg M, French SW (1996) Role of cytochrome P4502E1-dependent formation of hydroxyethyl free radical in the development of liver damage in rats intragastrically fed with ethanol. Hepatology 23(1):155–163

    Article  PubMed  CAS  Google Scholar 

  • Aleynik MK, Lieber CS (2001) Dilinoleoylphosphatidylcholine decreases ethanol-induced cytochrome P4502E1. Biochem Biophys Res Commun 288(4):1047–1051

    Article  PubMed  CAS  Google Scholar 

  • Aleynik MK, Leo MA, Aleynik SI, Lieber CS (1999) Polyenylphosphatidylcholine opposes the increase of cytochrome P-4502E1 by ethanol and corrects its iron-induced decrease. Alcohol Clin Exp Res 23(1):96–100

    Article  PubMed  CAS  Google Scholar 

  • Anandatheerthavarada HK, Shankar SK, Bhamre S, Boyd MR, Song BJ, Ravindranath V (1993) Induction of brain cytochrome P-450IIE1 by chronic ethanol treatment. Brain Res 601(1–2):279–285

    Article  PubMed  CAS  Google Scholar 

  • Andersen MR, Farin FM, Omiecinski CJ (1998) Quantification of multiple human cytochrome P450 mRNA molecules using competitive reverse transcriptase-PCR. DNA Cell Biol 17(3):231–238

    Article  PubMed  CAS  Google Scholar 

  • Arinç E, Arslan S, Adali O (2005) Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch Toxicol 79(8):427–433

    Article  PubMed  CAS  Google Scholar 

  • Arinç E, Arslan S, Bozcaarmutlu A, Adali O (2007) Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung. Food Chem Toxicol 45(1):107–118

    Article  PubMed  CAS  Google Scholar 

  • Asai H, Imaoka S, Kuroki T, Monna T, Funae Y (1996) Microsomal ethanol oxidizing system activity by human hepatic cytochrome P450s. J Pharmacol Exp Ther 277(2):1004–1009

    PubMed  CAS  Google Scholar 

  • Bae MA, Pie JE, Song BJ (2001) Acetaminophen induces apoptosis of C6 glioma cells by activating the c-Jun NH(2)-terminal protein kinase-related cell death pathway. Mol Pharmacol 60(4):847–856

    PubMed  CAS  Google Scholar 

  • Bai J, Cederbaum AI (2004) Adenovirus mediated overexpression of CYP2E1 increases sensitivity of HepG2 cells to acetaminophen induced cytotoxicity. Mol Cell Biochem 262(1–2):165–176

    Article  PubMed  CAS  Google Scholar 

  • Bai J, Cederbaum AI (2006) Overexpression of CYP2E1 in mitochondria sensitizes HepG2 cells to the toxicity caused by depletion of glutathione. J Biol Chem 281(8):5128–5136

    Article  PubMed  CAS  Google Scholar 

  • Bailey SM, Mantena SK, Millender-Swain T, Cakir Y, Jhala NC, Chhieng D, Pinkerton KE, Ballinger SW (2009) Ethanol and tobacco smoke increase hepatic steatosis and hypoxia in the hypercholesterolemic apoE(−/−) mouse: implications for a “multihit” hypothesis of fatty liver disease. Free Radic Biol Med 46(7):928–938

    Article  PubMed  CAS  Google Scholar 

  • Bansal S, Liu CP, Sepuri NB, Anandatheerthavarada HK, Selvaraj V, Hoek J, Milne GL, Guengerich FP, Avadhani NG (2010) Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress. J Biol Chem 285(32):24609–24619

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce F, Yuan QX, Li J, French BA, Fang C, Ingelman-Sundberg M, French SW (2000) The effect of ethanol-induced cytochrome p4502E1 on the inhibition of proteasome activity by alcohol. Biochem Biophys Res Commun 279(1):23–29

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce F, Li J, French BA, French SW (2002) Ethanol withdrawal induced CYP2E1 degradation in vivo, blocked by proteasomal inhibitor PS-341. Free Radic Biol Med 32(1):17–21

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce F, Wilson L, Nan L, Li J, French BA, Morgan TR, Morgan K, French SW (2005) CYP2E1 inhibition enhances mallory body formation. Exp Mol Pathol 78(3):207–211

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce F, French BA, Nan L, Song H, Nguyen SK, Yong H, Dede J, French SW (2006) CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation. Exp Mol Pathol 81(3):191–201

    Article  PubMed  CAS  Google Scholar 

  • Baumgardner JN, Shankar K, Korourian S, Badger TM, Ronis MJ (2007) Undernutrition enhances alcohol-induced hepatocyte proliferation in the liver of rats fed via total enteral nutrition. Am J Physiol Gastrointest Liver Physiol 293(1):G355–G364

    Article  PubMed  CAS  Google Scholar 

  • Baumgardner JN, Shankar K, Hennings L, Badger TM, Ronis MJ (2008) A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet. Am J Physiol Gastrointest Liver Physiol 294(1):G27–G38

    Article  PubMed  CAS  Google Scholar 

  • Bhagwat SV, Boyd MR, Ravindranath V (1995) Brain mitochondrial cytochromes P450: xenobiotic metabolism, presence of multiple forms and their selective inducibility. Arch Biochem Biophys 320(1):73–83

    Article  PubMed  CAS  Google Scholar 

  • Boutelet-Bochan H, Huang Y, Juchau MR (1997) Expression of CYP2E1 during embryogenesis and fetogenesis in human cephalic tissues: implications for the fetal alcohol syndrome. Biochem Biophys Res Commun 238(2):443–447

    Article  PubMed  CAS  Google Scholar 

  • Bradford BU, Kono H, Isayama F, Kosyk O, Wheeler MD, Akiyama TE, Bleye L, Krausz KW, Gonzalez FJ, Koop DR, Rusyn I (2005) Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver. Hepatology 41(2):336–344

    Article  PubMed  CAS  Google Scholar 

  • Brzezinski MR, Boutelet-Bochan H, Person RE, Fantel AG, Juchau MR (1999) Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain. J Pharmacol Exp Ther 289(3):1648–1653

    PubMed  CAS  Google Scholar 

  • Bühler R, Lindros KO, von Boguslawsky K, Kärkkäinen P, Mäkinen J, Ingelman-Sundberg M (1991) Perivenous expression of ethanol-inducible cytochrome P450 IIE1 in livers from alcoholics and chronically ethanol-fed rats. Alcohol Alcohol Suppl 1:311–315

    PubMed  Google Scholar 

  • Bühler R, Lindros KO, Nordling A, Johansson I, Ingelman-Sundberg M (1992) Zonation of cytochrome P450 isozyme expression and induction in rat liver. Eur J Biochem 204(1):407–412

    Article  PubMed  Google Scholar 

  • Butura A, Nilsson K, Morgan K, Morgan TR, French SW, Johansson I, Schuppe-Koistinen I, Ingelman-Sundberg M (2009) The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model. J Hepatol 50(3):572–583

    Article  PubMed  CAS  Google Scholar 

  • Cao Q, Mak KM, Lieber CS (2005) Cytochrome P4502E1 primes macrophages to increase TNF-alpha production in response to lipopolysaccharide. Am J Physiol Gastrointest Liver Physiol 289(1):G95–G107

    Article  PubMed  CAS  Google Scholar 

  • Caro AA, Cederbaum AI (2001) Synergistic toxicity of iron and arachidonic acid in HepG2 cells overexpressing CYP2E1. Mol Pharmacol 60(4):742–752

    PubMed  CAS  Google Scholar 

  • Caro AA, Cederbaum AI (2002a) Role of calcium and calcium-activated proteases in CYP2E1-dependent toxicity in HEPG2 cells. J Biol Chem 277(1):104–113

    Article  PubMed  CAS  Google Scholar 

  • Caro AA, Cederbaum AI (2002b) Ca2+-dependent and independent mitochondrial damage in HepG2 cells that overexpress CYP2E1. Arch Biochem Biophys 408(2):162–170

    Article  PubMed  CAS  Google Scholar 

  • Caro AA, Cederbaum AI (2003) Role of phospholipase A2 activation and calcium in CYP2E1-dependent toxicity in HepG2 cells. J Biol Chem 278(36):33866–33877

    Article  PubMed  CAS  Google Scholar 

  • Caro AA, Evans KL, Cederbaum AI (2009) CYP2E1 overexpression inhibits microsomal Ca2+-ATPase activity in HepG2 cells. Toxicology 255(3):171–176

    Article  PubMed  CAS  Google Scholar 

  • Carpenter SP, Lasker JM, Raucy JL (1996) Expression, induction, and catalytic activity of the ethanol-inducible cytochrome P450 (CYP2E1) in human fetal liver and hepatocytes. Mol Pharmacol 49(2):260–268

    PubMed  CAS  Google Scholar 

  • Carpenter SP, Savage DD, Schultz ED, Raucy JL (1997) Ethanol-mediated transplacental induction of CYP2E1 in fetal rat liver. J Pharmacol Exp Ther 282(2):1028–1036

    PubMed  CAS  Google Scholar 

  • Carroccio A, Wu D, Cederbaum AI (1994) Ethanol increases content and activity of human cytochrome P4502E1 in a transduced HepG2 cell line. Biochem Biophys Res Commun 203(1):727–733

    Article  PubMed  CAS  Google Scholar 

  • Castillo T, Koop DR, Kamimura S, Triadafilopoulos G, Tsukamoto H (1992) Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Hepatology 16(4):992–996

    Article  PubMed  CAS  Google Scholar 

  • Cederbaum AI (1991) Microsomal generation of reactive oxygen species and their possible role in alcohol hepatotoxicity. Alcohol Alcohol Suppl 1:291–296

    PubMed  CAS  Google Scholar 

  • Cederbaum AI (2010) Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury. World J Gastroenterol 16(11):1366–1376

    Article  PubMed  CAS  Google Scholar 

  • Chalasani N, Gorski JC, Asghar MS, Asghar A, Foresman B, Hall SD, Crabb DW (2003) Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 37(3):544–550

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekaran K, Swaminathan K, Kumar SM, Chatterjee S, Clemens DL, Dey A (2011) Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes – alcohol dehydrogenase and Cytochrome P450 2E1. Toxicol In Vitro 25(4):969–978

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekaran K, Swaminathan K, Kumar SM, Clemens DL, Dey A (2012a) Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose. Integr Biol (Camb) 4(5):550–563

    Article  CAS  Google Scholar 

  • Chandrasekaran K, Swaminathan K, Mathan Kumar S, Clemens DL, Dey A (2012b) In vitro evidence for chronic alcohol and high glucose mediated increased oxidative stress and hepatotoxicity. Alcohol Clin Exp Res 36(6):487–495

    Article  CAS  Google Scholar 

  • Chang TK, Crespi CL, Waxman DJ (2006) Spectrophotometric analysis of human CYP2E1-catalyzed p-nitrophenol hydroxylation. Methods Mol Biol 320:127–131

    PubMed  CAS  Google Scholar 

  • Chen Q, Cederbaum AI (1998) Cytotoxicity and apoptosis produced by cytochrome P450 2E1 in Hep G2 cells. Mol Pharmacol 53(4):638–648

    PubMed  CAS  Google Scholar 

  • Chen Q, Galleano M, Cederbaum AI (1997) Cytotoxicity and apoptosis produced by arachidonic acid in Hep G2 cells overexpressing human cytochrome P4502E1. J Biol Chem 272(23):14532–14541

    Article  PubMed  CAS  Google Scholar 

  • Chen GF, Ronis MJ, Ingelman-Sundberg M, Badger TM (1999) Hormonal regulation of microsomal cytochrome P4502E1 and P450 reductase in rat liver and kidney. Xenobiotica 29(5):437–451

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Krausz KW, Idle JR, Gonzalez FJ (2008) Identification of novel toxicity-associated metabolites by metabolomics and mass isotopomer analysis of acetaminophen metabolism in wild-type and Cyp2e1-null mice. J Biol Chem 283(8):4543–4559

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Krausz KW, Shah YM, Idle JR, Gonzalez FJ (2009) Serum metabolomics reveals irreversible inhibition of fatty acid beta-oxidation through the suppression of PPARalpha activation as a contributing mechanism of acetaminophen-induced hepatotoxicity. Chem Res Toxicol 22(4):699–707

    Article  PubMed  CAS  Google Scholar 

  • Cheng PY, Wang M, Morgan ET (2003) Rapid transcriptional suppression of rat cytochrome P450 genes by endotoxin treatment and its inhibition by curcumin. J Pharmacol Exp Ther 307(3):1205–1212

    Article  PubMed  CAS  Google Scholar 

  • Cheung C, Akiyama TE, Kudo G, Gonzalez FJ (2003) Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1alpha)-deficient mice. Biochem Pharmacol 66(10):2011–2020

    Article  PubMed  CAS  Google Scholar 

  • Cheung C, Yu AM, Ward JM, Krausz KW, Akiyama TE, Feigenbaum L, Gonzalez FJ (2005) The cyp2e1-humanized transgenic mouse: role of cyp2e1 in acetaminophen hepatotoxicity. Drug Metab Dispos 33(3):449–457

    Article  PubMed  CAS  Google Scholar 

  • Chilakapati J, Korrapati MC, Shankar K, Hill RA, Warbritton A, Latendresse JR, Mehendale HM (2007) Role of CYP2E1 and saturation kinetics in the bioactivation of thioacetamide: effects of diet restriction and phenobarbital. Toxicol Appl Pharmacol 219(1):72–84

    Article  PubMed  CAS  Google Scholar 

  • Clot P, Albano E, Eliasson E, Tabone M, Aricò S, Israel Y, Moncada C, Ingelman-Sundberg M (1996) Cytochrome P4502E1 hydroxyethyl radical adducts as the major antigen in autoantibody formation among alcoholics. Gastroenterology 111(1):206–216

    Article  PubMed  CAS  Google Scholar 

  • Clot P, Parola M, Bellomo G, Dianzani U, Carini R, Tabone M, Aricò S, Ingelman-Sundberg M, Albano E (1997) Plasma membrane hydroxyethyl radical adducts cause antibody-dependent cytotoxicity in rat hepatocytes exposed to alcohol. Gastroenterology 113(1):265–276

    Article  PubMed  CAS  Google Scholar 

  • Correa M, Viaggi C, Escrig MA, Pascual M, Guerri C, Vaglini F, Aragon CM, Corsini GU (2009) Ethanol intake and ethanol-induced locomotion and locomotor sensitization in Cyp2e1 knockout mice. Pharmacogenet Genomics 19(3):217–225

    Article  PubMed  CAS  Google Scholar 

  • Cummings BS, Zangar RC, Novak RF, Lash LH (1999) Cellular distribution of cytochromes P-450 in the rat kidney. Drug Metab Dispos 27(4):542–548

    PubMed  CAS  Google Scholar 

  • Cummings BS, Parker JC, Lash LH (2001) Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney. Toxicol Sci 60(1):11–19

    Article  PubMed  CAS  Google Scholar 

  • Curry-McCoy TV, Osna NA, Nanji AA, Donohue TM Jr (2010) Chronic ethanol consumption results in atypical liver injury in copper/zinc superoxide dismutase deficient mice. Alcohol Clin Exp Res 34(2):251–261

    Article  PubMed  CAS  Google Scholar 

  • Dai Y, Cederbaum AI (1995) Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J Pharmacol Exp Ther 273(3):1497–1505

    PubMed  CAS  Google Scholar 

  • Dai Y, Rashba-Step J, Cederbaum AI (1993) Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates. Biochemistry 32(27):6928–6937

    Article  PubMed  CAS  Google Scholar 

  • Daly AK, King BP, Leathart JB (2006) Genotyping for cytochrome P450 polymorphisms. Methods Mol Biol 320:193–207

    PubMed  CAS  Google Scholar 

  • Demeilliers C, Maisonneuve C, Grodet A, Mansouri A, Nguyen R, Tinel M, Lettéron P, Degott C, Feldmann G, Pessayre D, Fromenty B (2002) Impaired adaptive resynthesis and prolonged depletion of hepatic mitochondrial DNA after repeated alcohol binges in mice. Gastroenterology 123(4):1278–1290

    Article  PubMed  CAS  Google Scholar 

  • Dey A, Cederbaum AI (2006) Geldanamycin, an inhibitor of Hsp90, potentiates cytochrome P4502E1-mediated toxicity in HepG2 cells. J Pharmacol Exp Ther 317(3):1391–1399

    Article  PubMed  CAS  Google Scholar 

  • Dey A, Cederbaum AI (2007) Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/obmice. Hepatology 45(6):1355–1365

    Article  PubMed  CAS  Google Scholar 

  • Dey A, Parmar D, Dhawan A, Dash D, Seth PK (2002) Cytochrome P450 2E1 dependent catalytic activity and lipid peroxidation in rat blood lymphocytes. Life Sci 71(21):2509–2519

    Article  PubMed  CAS  Google Scholar 

  • Dey A, Dhawan A, Kishore Seth P, Parmar D (2005) Evidence for cytochrome P450 2E1 catalytic activity and expression in rat blood lymphocytes. Life Sci 77(10):1082–1093

    Article  PubMed  CAS  Google Scholar 

  • Dey A, Kessova IG, Cederbaum AI (2006) Decreased protein and mRNA expression of ER stress proteins GRP78 and GRP94 in HepG2 cells over-expressing CYP2E1. Arch Biochem Biophys 447(2):155–166

    Article  PubMed  CAS  Google Scholar 

  • Donohue TM, Osna NA, Clemens DL (2006) Recombinant HepG2 cells that express alcohol dehydrogenase and cytochrome P450 2E1 as a model of ethanol-elicited cytotoxicity. Int J Biochem Cell Biol 38(1):92–101

    Article  PubMed  CAS  Google Scholar 

  • Dupont I, Lucas D, Clot P, Ménez C, Albano E (1998) Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics. J Hepatol 28(4):564–571

    Article  PubMed  CAS  Google Scholar 

  • Ekström G, Ingelman-Sundberg M (1989) Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem Pharmacol 38(8):1313–1319

    Article  PubMed  Google Scholar 

  • El Hadri L, Chanas B, Ghanayem BI (2005) Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome P4502E1 and microsomal epoxide hydrolase-null mice. Toxicol Appl Pharmacol 205(2):116–125

    Article  PubMed  CAS  Google Scholar 

  • Eliasson E, Mkrtchian S, Ingelman-Sundberg M (1992) Hormone- and substrate-regulated intracellular degradation of cytochrome P450 (2E1) involving MgATP-activated rapid proteolysis in the endoplasmic reticulum membranes. J Biol Chem 267(22):15765–15769

    PubMed  CAS  Google Scholar 

  • Esfandiari F, Villanueva JA, Wong DH, French SW, Halsted CH (2005) Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol 289(1):G54–G63

    Article  PubMed  CAS  Google Scholar 

  • Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK (1998) Detection and characterization of novel polymorphisms in the CYP2E1 gene. Pharmacogenetics 8(6):543–552

    Article  PubMed  CAS  Google Scholar 

  • Fang C, Lindros KO, Badger TM, Ronis MJ, Ingelman-Sundberg M (1998) Zonated expression of cytokines in rat liver: effect of chronic ethanol and the cytochrome P450 2E1 inhibitor, chlormethiazole. Hepatology 27(5):1304–1310

    Article  PubMed  CAS  Google Scholar 

  • Farin FM, Omiecinski CJ (1993) Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue. J Toxicol Environ Health 40(2–3):317–335

    Article  PubMed  CAS  Google Scholar 

  • Farin FM, Pohlman TH, Omiecinski CJ (1994) Expression of cytochrome P450s and microsomal epoxide hydrolase in primary cultures of human umbilical vein endothelial cells. Toxicol Appl Pharmacol 124(1):1–9

    Article  PubMed  CAS  Google Scholar 

  • Farin FM, Bigler LG, Oda D, McDougall JK, Omiecinski CJ (1995) Expression of cytochrome P450 and microsomal epoxide hydrolase in cervical and oral epithelial cells immortalized by human papillomavirus type 16 E6/E7 genes. Carcinogenesis 16(6):1391–1401, Erratum in Carcinogenesis 16(7):1670

    Article  PubMed  CAS  Google Scholar 

  • Ferguson C, Miksys S, Palmour R, Tyndale RF (2011) Independent and combined effects of ethanol self-administration and nicotine treatment on hepatic CYP2E1 in African green monkeys. Drug Metab Dispos 39(12):2233–2241

    Article  PubMed  CAS  Google Scholar 

  • Fernández V, Massa L, Quiñones L, Simon-Giavarotti KA, Giavarotti L, D’Almeida V, Azzalis LA, Junqueira VB, Videla LA (2003) Effects of gamma-hexachlorocyclohexane and L-3,3′,5-triiodothyronine on rat liver cytochrome P4502E1-dependent activity and content in relation to microsomal superoxide radical generation. Biol Res 36(3–4):359–365

    PubMed  Google Scholar 

  • French SW, Wong K, Jui L, Albano E, Hagbjork AL, Ingelman-Sundberg M (1993) Effect of ethanol on cytochrome P450 2E1 (CYP2E1), lipid peroxidation, and serum protein adduct formation in relation to liver pathology pathogenesis. Exp Mol Pathol 58(1):61–75

    Article  PubMed  CAS  Google Scholar 

  • Garige M, Gong M, Rao MN, Zhang Y, Lakshman MR (2005) Mechanism of action of ethanol in the down-regulation of Gal(beta)1, 4GlcNAc alpha2,6-sialyltransferase messenger RNA in human liver cell lines. Metabolism 54(6):729–734

    Article  PubMed  CAS  Google Scholar 

  • Garner CE, Sloan C, Sumner SC, Burgess J, Davis J, Etheridge A, Parham A, Ghanayem BI (2007) CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice. Biol Reprod 76(3):496–505

    Article  PubMed  CAS  Google Scholar 

  • Garro AJ, Seitz HK, Lieber CS (1981) Enhancement of dimethylnitrosamine metabolism and activation to a mutagen following chronic ethanol consumption. Cancer Res 41(1):120–124

    PubMed  CAS  Google Scholar 

  • Gebhardt AC, Lucas D, Ménez JF, Seitz HK (1997) Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans. Hepatology 26(4):957–961

    Article  PubMed  CAS  Google Scholar 

  • Ghanayem BI (2007) Inhibition of urethane-induced carcinogenicity in cyp2e1−/− in comparison to cyp2e1+/+ mice. Toxicol Sci 95(2):331–339

    Article  PubMed  CAS  Google Scholar 

  • Ghanayem BI, Sanders JM, Chanas B, Burka LT, Gonzalez FJ (1999) Role of cytochrome P-450 2E1 in methacrylonitrile metabolism and disposition. J Pharmacol Exp Ther 289(2):1054–1059

    PubMed  CAS  Google Scholar 

  • Ghanayem BI, Witt KL, El-Hadri L, Hoffler U, Kissling GE, Shelby MD, Bishop JB (2005a) Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect. Biol Reprod 72(1):157–163

    Article  PubMed  CAS  Google Scholar 

  • Ghanayem BI, Witt KL, Kissling GE, Tice RR, Recio L (2005b) Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: evidence consistent with a glycidamide-mediated effect. Mutat Res 578(1–2):284–297

    PubMed  CAS  Google Scholar 

  • Ghanayem BI, McDaniel LP, Churchwell MI, Twaddle NC, Snyder R, Fennell TR, Doerge DR (2005c) Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts. Toxicol Sci 8(2):311–318

    Article  CAS  Google Scholar 

  • Gonzalez FJ (2005) Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res 569:101–110

    Article  PubMed  CAS  Google Scholar 

  • Gorsky LD, Koop DR, Coon MJ (1984) On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 259(11):6812–6817

    PubMed  CAS  Google Scholar 

  • Gouillon ZQ, Miyamoto K, Donohue TM, Wan YJ, French BA, Nagao Y, Fu P, Reitz RC, Hagbjork A, Yap C, Yuan QX, Ingelman-Sundberg M, French SW (1999) Role of CYP2E1 in the pathogenesis of alcoholic liver disease: modifications by cAMP and ubiquitin-proteasome pathway. Front Biosci 4:A16–A25

    Article  PubMed  CAS  Google Scholar 

  • Gouillon Z, Lucas D, Li J, Hagbjork AL, French BA, Fu P, Fang C, Ingelman-Sundberg M, Donohue TM Jr, French SW (2000) Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole. Proc Soc Exp Biol Med 224(4):302–308

    Article  PubMed  CAS  Google Scholar 

  • Grove J, Brown AS, Daly AK, Bassendine MF, James OF, Day CP (1998) The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype. Pharmacogenetics 8(4):335–342

    Article  PubMed  CAS  Google Scholar 

  • Gut I, Nedelcheva V, Soucek P, Stopka P, Vodicka P, Gelboin HV, Ingelman-Sundberg M (1996) The role of CYP2E1 and 2B1 in metabolic activation of benzene derivatives. Arch Toxicol 71(1–2):45–56

    Article  PubMed  CAS  Google Scholar 

  • Hase I, Imaoka S, Oda Y, Hiroi T, Nakamoto T, Asada A, Funae Y (2000) Area under the plasma concentration-time curve of inorganic fluoride following sevoflurane anesthesia correlates with CYP2E1 mRNA level in mononuclear cells. Anesthesiology 92(6):1661–1666

    Article  PubMed  CAS  Google Scholar 

  • Hoffler U, Ghanayem BI (2005) Increased bioaccumulation of urethane in CYP2E1−/− versus CYP2E1+/+ mice. Drug Metab Dispos 33(8):1144–1150

    Article  PubMed  CAS  Google Scholar 

  • Hoffler U, El-Masri HA, Ghanayem BI (2003) Cytochrome P450 2E1 (CYP2E1) is the principal enzyme responsible for urethane metabolism: comparative studies using CYP2E1-null and wild-type mice. J Pharmacol Exp Ther 305(2):557–564

    Article  PubMed  CAS  Google Scholar 

  • Hoffler U, Dixon D, Peddada S, Ghanayem BI (2005) Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice. Mutat Res 572(1–2):58–72

    PubMed  CAS  Google Scholar 

  • Howard LA, Micu AL, Sellers EM, Tyndale RF (2001) Low doses of nicotine and ethanol induce CYP2E1 and chlorzoxazone metabolism in rat liver. J Pharmacol Exp Ther 299(2):542–550

    PubMed  CAS  Google Scholar 

  • Howard LA, Miksys S, Hoffmann E, Mash D, Tyndale RF (2003a) Brain CYP2E1 is induced by nicotine and ethanol in rat and is higher in smokers and alcoholics. Br J Pharmacol 138(7):1376–1386

    Article  PubMed  CAS  Google Scholar 

  • Howard LA, Ahluwalia JS, Lin SK, Sellers EM, Tyndale RF (2003b) CYP2E1*1D regulatory polymorphism: association with alcohol and nicotine dependence. Pharmacogenetics 13(6):321–328

    Article  PubMed  CAS  Google Scholar 

  • Hu Y, Mishin V, Johansson I, von Bahr C, Cross A, Ronis MJ, Badger TM, Ingelman-Sundberg M (1994) Chlormethiazole as an efficient inhibitor of cytochrome P450 2E1 expression in rat liver. J Pharmacol Exp Ther 269(3):1286–1291

    PubMed  CAS  Google Scholar 

  • Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arincò S, Albano E, Ingelman-Sundberg M (1997) Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol Pharmacol 51(3):370–376

    PubMed  CAS  Google Scholar 

  • Hu Y, Hakkola J, Oscarson M, Ingelman-Sundberg M (1999) Structural and functional characterization of the 5′-flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene. Biochem Biophys Res Commun 263(2):286–293

    Article  PubMed  CAS  Google Scholar 

  • Huan JY, Koop DR (1999) Tightly regulated and inducible expression of rabbit CYP2E1 using a tetracycline-controlled expression system. Drug Metab Dispos 27(4):549–554

    PubMed  CAS  Google Scholar 

  • Huan JY, Streicher JM, Bleyle LA, Koop DR (2004) Proteasome-dependent degradation of cytochromes P450 2E1 and 2B1 expressed in tetracycline-regulated HeLa cells. Toxicol Appl Pharmacol 199(3):332–343

    Article  PubMed  CAS  Google Scholar 

  • Jeong KS, Soh Y, Jeng J, Felder MR, Hardwick JP, Song BJ (2000) Cytochrome P450 2E1 (CYP2E1)-dependent production of a 37-kDa acetaldehyde-protein adduct in the rat liver. Arch Biochem Biophys 384(1):81–87

    Article  PubMed  CAS  Google Scholar 

  • Johansson I, Lindros KO, Eriksson H, Ingelman-Sundberg M (1990) Transcriptional control of CYP2E1 in the perivenous liver region and during starvation. Biochem Biophys Res Commun 173(1):331–338

    Article  PubMed  CAS  Google Scholar 

  • Johansson I, Eliasson E, Ingelman-Sundberg M (1991) Hormone controlled phosphorylation and degradation of CYP2B1 and CYP2E1 in isolated rat hepatocytes. Biochem Biophys Res Commun 174(1):37–42

    Article  PubMed  CAS  Google Scholar 

  • Johri A, Yadav S, Dhawan A, Parmar D (2007) Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane. Toxicol Appl Pharmacol 225(3):278–292

    Article  PubMed  CAS  Google Scholar 

  • Jones BE, Liu H, Lo CR, Koop DR, Czaja MJ (2002) Cytochrome P450 2E1 expression induces hepatocyte resistance to cell death from oxidative stress. Antioxid Redox Signal 4(5):701–709

    Article  PubMed  CAS  Google Scholar 

  • Joshi M, Tyndale RF (2006a) Regional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine. Neuropharmacology 50(5):568–575

    Article  PubMed  CAS  Google Scholar 

  • Joshi M, Tyndale RF (2006b) Induction and recovery time course of rat brain CYP2E1 after nicotine treatment. Drug Metab Dispos 34(4):647–652

    Article  PubMed  CAS  Google Scholar 

  • Kapoor N, Pant AB, Dhawan A, Dwievedi UN, Gupta YK, Seth PK, Parmar D (2006) Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol. Life Sci 79(16):1514–1522

    Article  PubMed  CAS  Google Scholar 

  • Kathirvel E, Morgan K, French SW, Morgan TR (2009) Overexpression of liver-specific cytochrome P4502E1 impairs hepatic insulin signaling in a transgenic mouse model of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 21(9):973–983

    Article  PubMed  CAS  Google Scholar 

  • Kathirvel E, Chen P, Morgan K, French SW, Morgan TR (2010) Oxidative stress and regulation of anti-oxidant enzymes in cytochrome P4502E1 transgenic mouse model of non-alcoholic fatty liver. J Gastroenterol Hepatol 25(6):1136–1143

    Article  PubMed  CAS  Google Scholar 

  • Kessova IG, Cederbaum AI (2007) Mitochondrial alterations in livers of Sod1−/− mice fed alcohol. Free Radic Biol Med 42(10):1470–1480

    Article  PubMed  CAS  Google Scholar 

  • Kessova IG, DeCarli LM, Lieber CS (1998) Inducibility of cytochromes P-4502E1 and P-4501A1 in the rat pancreas. Alcohol Clin Exp Res 22(2):501–504

    Article  PubMed  CAS  Google Scholar 

  • Kessova IG, Leo MA, Lieber CS (2001) Effect of beta-carotene on hepatic cytochrome P-450 in ethanol-fed rats. Alcohol Clin Exp Res 25(9):1368–1372

    PubMed  CAS  Google Scholar 

  • Khalighi M, Brzezinski MR, Chen H, Juchau MR (1999) Inhibition of human prenatal biosynthesis of all-trans-retinoic acid by ethanol, ethanol metabolites, and products of lipid peroxidation reactions: a possible role for CYP2E1. Biochem Pharmacol 57(7):811–821

    Article  PubMed  CAS  Google Scholar 

  • Khan AJ, Ruwali M, Choudhuri G, Mathur N, Husain Q, Parmar D (2009) Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis. Mutat Res 664(1–2):55–63

    PubMed  CAS  Google Scholar 

  • Khan AJ, Husain Q, Choudhuri G, Parmar D (2010) Association of polymorphism in alcohol dehydrogenase and interaction with other genetic risk factors with alcoholic liver cirrhosis. Drug Alcohol Depend 109(1–3):190–197

    Article  PubMed  CAS  Google Scholar 

  • Khan AJ, Sharma A, Choudhuri G, Parmar D (2011) Induction of blood lymphocyte cytochrome P450 2E1 in early stage alcoholic liver cirrhosis. Alcohol 45(1):81–87

    Article  PubMed  CAS  Google Scholar 

  • Khemawoot P, Yokogawa K, Shimada T, Miyamoto K (2007a) Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats. Biochem Pharmacol 73(1):155–162

    Article  PubMed  CAS  Google Scholar 

  • Khemawoot P, Nishino K, Ishizaki J, Yokogawa K, Miyamoto K (2007b) Circadian rhythm of cytochrome P4502E1 and its effect on disposition kinetics of chlorzoxazone in rats. Eur J Pharmacol 574(1):71–76

    Article  PubMed  CAS  Google Scholar 

  • Kim BJ, Hood BL, Aragon RA, Hardwick JP, Conrads TP, Veenstra TD, Song BJ (2006) Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells. Proteomics 6(4):1250–1260

    Article  PubMed  CAS  Google Scholar 

  • Knockaert L, Descatoire V, Vadrot N, Fromenty B, Robin MA (2011) Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen. Toxicol In Vitro 25(2):475–484

    Article  PubMed  CAS  Google Scholar 

  • Kocarek TA, Zangar RC, Novak RF (2000) Post-transcriptional regulation of rat CYP2E1 expression: role of CYP2E1 mRNA untranslated regions in control of translational efficiency and message stability. Arch Biochem Biophys 376(1):180–190

    Article  PubMed  CAS  Google Scholar 

  • Koivisto T, Mishin VM, Mak KM, Cohen PA, Lieber CS (1996) Induction of cytochrome P-4502E1 by ethanol in rat Kupffer cells. Alcohol Clin Exp Res 20(2):207–212

    Article  PubMed  CAS  Google Scholar 

  • Konishi M, Ishii H (2007) Role of microsomal enzymes in development of alcoholic liver diseases. J Gastroenterol Hepatol 22(Suppl 1):S7–S10

    Article  PubMed  CAS  Google Scholar 

  • Koop DR (1992) Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 6:724–730

    PubMed  CAS  Google Scholar 

  • Koop DR (2006) Alcohol metabolism’s damaging effects on the cell: a focus on reactive oxygen generation by the enzyme cytochrome P450 2E1. Alcohol Res Health 29(4):274–280

    PubMed  Google Scholar 

  • Koop DR, Tierney DJ (1990) Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. Bioessays 12(9):429–435

    Article  PubMed  CAS  Google Scholar 

  • Koop DR, Morgan ET, Tarr CE, Coon MJ (1982) Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits. J Biol Chem 257:8472–8480

    PubMed  CAS  Google Scholar 

  • Koop DR, Chernosky A, Brass EP (1991) Identification and induction of cytochrome P450 2E1 in rat Kupffer cells. J Pharmacol Exp Ther 258(3):1072–1076

    PubMed  CAS  Google Scholar 

  • Korourian S, Hakkak R, Ronis MJ, Shelnutt SR, Waldron J, Ingelman-Sundberg M, Badger TM (1999) Diet and risk of ethanol-induced hepatotoxicity: carbohydrate-fat relationships in rats. Toxicol Sci 47(1):110–117

    Article  PubMed  CAS  Google Scholar 

  • Kraner JC, Lasker JM, Corcoran GB, Ray SD, Raucy JL (1993) Induction of P4502E1 by acetone in isolated rabbit hepatocytes. Role of increased protein and mRNA synthesis. Biochem Pharmacol 45(7):1483–1492

    Article  PubMed  CAS  Google Scholar 

  • Kukielka E, Cederbaum AI (1994) DNA strand cleavage as a sensitive assay for the production of hydroxyl radicals by microsomes: role of cytochrome P4502E1 in the increased activity after ethanol treatment. Biochem J 302(Pt 3):773–779

    PubMed  CAS  Google Scholar 

  • Kunitoh S, Imaoka S, Hiroi T, Yabusaki Y, Monna T, Funae Y (1997) Acetaldehyde as well as ethanol is metabolized by human CYP2E1. J Pharmacol Exp Ther 280(2):527–532

    PubMed  CAS  Google Scholar 

  • Lagadic-Gossmann D, Lerche C, Rissel M, Joannard F, Galisteo M, Guillouzo A, Corcos L (2000) The induction of the human hepatic CYP2E1 gene by interleukin 4 is transcriptional and regulated by protein kinase C. Cell Biol Toxicol 16(4):221–233

    Article  PubMed  CAS  Google Scholar 

  • Lash LH, Putt DA, Huang P, Hueni SE, Parker JC (2007) Modulation of hepatic and renal metabolism and toxicity of trichloroethylene and perchloroethylene by alterations in status of cytochrome P450 and glutathione. Toxicology 235(1–2):11–26

    Article  PubMed  CAS  Google Scholar 

  • Leclercq IA, Field J, Enriquez A, Farrell GC, Robertson GR (2000a) Constitutive and inducible expression of hepatic CYP2E1 in leptin-deficient ob/ob mice. Biochem Biophys Res Commun 268(2):337–344

    Article  PubMed  CAS  Google Scholar 

  • Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ, Robertson GR (2000b) CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 105(8):1067–1075

    Article  PubMed  CAS  Google Scholar 

  • Lee YS, Wan J, Kim BJ, Bae MA, Song BJ (2006a) Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen. J Pharmacol Exp Ther 317(1):202–208

    Article  PubMed  CAS  Google Scholar 

  • Lee AM, Yue J, Tyndale RF (2006b) In vivo and in vitro characterization of chlorzoxazone metabolism and hepatic CYP2E1 levels in African Green monkeys: induction by chronic nicotine treatment. Drug Metab Dispos 34(9):1508–1515

    Article  PubMed  CAS  Google Scholar 

  • Lee AM, Joshi M, Yue J, Tyndale RF (2006c) Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism. Eur J Pharmacol 552(1–3):151–158

    Article  PubMed  CAS  Google Scholar 

  • Lejus C, Fautrel A, Mallédant Y, Guillouzo A (2002) Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol 64(7):1151–1156

    Article  PubMed  CAS  Google Scholar 

  • Lerche C, Le Jossic C, Fautrel A, de Waziers I, Ballet F, Guillouzo A, Corcos L (1996) Rat liver epithelial cells express functional cytochrome P450 2E1. Carcinogenesis 17(5):1101–1106

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS (1993) Biochemical factors in alcoholic liver disease. Semin Liver Dis 13(2):136–153

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS (2004) The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. Drug Metab Rev 36(3–4):511–529

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS, DeCarli LM (1968) Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding. Science 162(3856):917–918

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C, Ponomarenko A, DeCarli LM (2004a) Acarbose attenuates experimental non-alcoholic steatohepatitis. Biochem Biophys Res Commun 315(3):699–703

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C, Ponomarenko A, DeCarli LM (2004b) Model of nonalcoholic steatohepatitis. Am J Clin Nutr 79(3):502–509

    PubMed  CAS  Google Scholar 

  • Lieber CS, Leo MA, Cao Q, Mak KM, Ren C, Ponomarenko A, Wang X, Decarli LM (2007a) The combination of S-adenosylmethionine and dilinoleoylphosphatidylcholine attenuates non-alcoholic steatohepatitis produced in rats by a high-fat diet. Nutr Res 27(9):565–573

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS, Cao Q, DeCarli LM, Leo MA, Mak KM, Ponomarenko A, Ren C, Wang X (2007b) Role of medium-chain triglycerides in the alcohol-mediated cytochrome P450 2E1 induction of mitochondria. Alcohol Clin Exp Res 31(10):1660–1668

    Article  PubMed  CAS  Google Scholar 

  • Liu C, Russell RM, Seitz HK, Wang XD (2001) Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1. Gastroenterology 120(1):179–189

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Jones BE, Bradham C, Czaja MJ (2002) Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-alpha. Am J Physiol Gastrointest Liver Physiol 282(2):G257–G266

    PubMed  CAS  Google Scholar 

  • Lu Y, Cederbaum AI (2006) Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol Sci 89(2):515–523

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Cederbaum AI (2008) CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 44(5):723–738

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Wang X, Cederbaum AI (2005) Lipopolysaccharide-induced liver injury in rats treated with the CYP2E1 inducer pyrazole. Am J Physiol Gastrointest Liver Physiol 289(2):G308–G319

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Zhuge J, Wang X, Bai J, Cederbaum AI (2008) Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology 47(5):1483–1494

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Wu D, Wang X, Ward SC, Cederbaum AI (2010) Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in mice. Free Radic Biol Med 49(9):1406–1416

    Article  PubMed  CAS  Google Scholar 

  • Lytton SD, Helander A, Zhang-Gouillon ZQ, Stokkeland K, Bordone R, Aricò S, Albano E, French SW, Ingelman-Sundberg M (1999) Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics. Mol Pharmacol 55(2):223–233

    PubMed  CAS  Google Scholar 

  • Ma XL, Baraona E, Lasker JM, Lieber CS (1991) Effects of ethanol consumption on bioactivation and hepatotoxicity of N-nitrosodimethylamine in rats. Biochem Pharmacol 42(3):585–591

    Article  PubMed  CAS  Google Scholar 

  • Maher JM, Slitt AL, Callaghan TN, Cheng X, Cheung C, Gonzalez FJ, Klaassen CD (2006) Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha. Biochem Pharmacol 72(4):512–522

    Article  PubMed  CAS  Google Scholar 

  • Mantena SK, Vaughn DP, Andringa KK, Eccleston HB, King AL, Abrams GA, Doeller JE, Kraus DW, Darley-Usmar VM, Bailey SM (2009) High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J 417(1):183–193

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Chantar ML, Corrales FJ, Martínez-Cruz LA, García-Trevijano ER, Huang ZZ, Chen L, Kanel G, Avila MA, Mato JM, Lu SC (2002) Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J 16(10):1292–1294

    PubMed  Google Scholar 

  • Menez JF, Machu TK, Song BJ, Browning MD, Deitrich RA (1993) Phosphorylation of cytochrome P4502E1 (CYP2E1) by calmodulin dependent protein kinase, protein kinase C and cAMP dependent protein kinase. Alcohol Alcohol 28(4):445–451

    PubMed  CAS  Google Scholar 

  • Mi LJ, Mak KM, Lieber CS (2000) Attenuation of alcohol-induced apoptosis of hepatocytes in rat livers by polyenylphosphatidylcholine (PPC). Alcohol Clin Exp Res 24(2):207–212

    Article  PubMed  CAS  Google Scholar 

  • Micu AL, Miksys S, Sellers EM, Koop DR, Tyndale RF (2003) Rat hepatic CYP2E1 is induced by very low nicotine doses: an investigation of induction, time course, dose response, and mechanism. J Pharmacol Exp Ther 306(3):941–947

    Article  PubMed  CAS  Google Scholar 

  • Millonig G, Wang Y, Homann N, Bernhardt F, Qin H, Mueller S, Bartsch H, Seitz HK (2011) Ethanol-mediated carcinogenesis in the human esophagus implicates CYP2E1 induction and the generation of carcinogenic DNA-lesions. Int J Cancer 128(3):533–540

    Article  PubMed  CAS  Google Scholar 

  • Mishin VM, Koivisto T, Lieber CS (1996) The determination of cytochrome P450 2E1-dependent p-nitrophenol hydroxylation by high-performance liquid chromatography with electrochemical detection. Anal Biochem 233(2):212–215

    Article  PubMed  CAS  Google Scholar 

  • Morgan ET (1993) Down-regulation of multiple cytochrome P450 gene products by inflammatory mediators in vivo. Independence from the hypothalamo-pituitary axis. Biochem Pharmacol 45(2):415–419

    Article  PubMed  CAS  Google Scholar 

  • Morgan ET, Thomas KB, Swanson R, Vales T, Hwang J, Wright K (1994) Selective suppression of cytochrome P-450 gene expression by interleukins 1 and 6 in rat liver. Biochim Biophys Acta 1219(2):475–483

    Article  PubMed  CAS  Google Scholar 

  • Morgan K, French SW, Morgan TR (2002) Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage. Hepatology 36(1):122–134

    Article  PubMed  CAS  Google Scholar 

  • Morimoto M, Hagbjörk AL, Nanji AA, Ingelman-Sundberg M, Lindros KO, Fu PC, Albano E, French SW (1993) Role of cytochrome P4502E1 in alcoholic liver disease pathogenesis. Alcohol 10(6):459–464

    Article  PubMed  CAS  Google Scholar 

  • Morimoto M, Zern MA, Hagbjörk AL, Ingelman-Sundberg M, French SW (1994) Fish oil, alcohol, and liver pathology: role of cytochrome P450 2E1. Proc Soc Exp Biol Med 207(2):197–205

    PubMed  CAS  Google Scholar 

  • Morimoto M, Reitz RC, Morin RJ, Nguyen K, Ingelman-Sundberg M, French SW (1995a) CYP-2E1 inhibitors partially ameliorate the changes in hepatic fatty acid composition induced in rats by chronic administration of ethanol and a high fat diet. J Nutr 125(12):2953–2964

    PubMed  CAS  Google Scholar 

  • Morimoto M, Hagbjörk AL, Wan YJ, Fu PC, Clot P, Albano E, Ingelman-Sundberg M, French SW (1995b) Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. Hepatology 21(6):1610–1617

    PubMed  CAS  Google Scholar 

  • Nanji AA, Zhao S, Lamb RG, Sadrzadeh SM, Dannenberg AJ, Waxman DJ (1993) Changes in microsomal phospholipases and arachidonic acid in experimental alcoholic liver injury: relationship to cytochrome P-450 2E1 induction and conjugated diene formation. Alcohol Clin Exp Res 17(3):598–603

    Article  PubMed  CAS  Google Scholar 

  • Nanji AA, Zhao S, Sadrzadeh SM, Dannenberg AJ, Tahan SR, Waxman DJ (1994) Markedly enhanced cytochrome P450 2E1 induction and lipid peroxidation is associated with severe liver injury in fish oil-ethanol-fed rats. Alcohol Clin Exp Res 18(5):1280–1285

    Article  PubMed  CAS  Google Scholar 

  • Neafsey P, Ginsberg G, Hattis D, Johns DO, Guyton KZ, Sonawane B (2009) Genetic polymorphism in CYP2E1: population distribution of CYP2E1 activity. J Toxicol Environ Health B Crit Rev 12(5–6):362–388

    PubMed  CAS  Google Scholar 

  • Nedelcheva V, Gut I, Soucek P, Tichavská B, Týnkova L, Mráz J, Guengerich FP, Ingelman-Sundberg M (1999) Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression. Arch Toxicol 73(1):33–40

    Article  PubMed  CAS  Google Scholar 

  • Nelson DR, Kamataki T, Waxman DJ, Guengerich FP, Estabrook RW, Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O et al (1993) The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12(1):1–51

    Article  PubMed  CAS  Google Scholar 

  • Neve EP, Ingelman-Sundberg M (1999) A soluble NH(2)-terminally truncated catalytically active form of rat cytochrome P450 2E1 targeted to liver mitochondria (1). FEBS Lett 460(2):309–314

    Article  PubMed  CAS  Google Scholar 

  • Neve EP, Ingelman-Sundberg M (2000) Molecular basis for the transport of cytochrome P450 2E1 to the plasma membrane. J Biol Chem 275(22):17130–17135

    Article  PubMed  CAS  Google Scholar 

  • Neve EP, Ingelman-Sundberg M (2001) Identification and characterization of a mitochondrial targeting signal in rat cytochrome P450 2E1 (CYP2E1). J Biol Chem 276(14):11317–11322

    Article  PubMed  CAS  Google Scholar 

  • Niemelä O, Parkkila S, Pasanen M, Iimuro Y, Bradford B, Thurman RG (1998) Early alcoholic liver injury: formation of protein adducts with acetaldehyde and lipid peroxidation products, and expression of CYP2E1 and CYP3A. Alcohol Clin Exp Res 22(9):2118–2124

    Article  PubMed  Google Scholar 

  • Niemelä O, Parkkila S, Pasanen M, Viitala K, Villanueva JA, Halsted CH (1999) Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs. Hepatology 30(4):1011–1017

    Article  PubMed  Google Scholar 

  • Nieto N, Friedman SL, Greenwel P, Cederbaum AI (1999) CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells. Hepatology 30(4):987–996

    Article  PubMed  CAS  Google Scholar 

  • Nieto N, Greenwel P, Friedman SL, Zhang F, Dannenberg AJ, Cederbaum AI (2000) Ethanol and arachidonic acid increase alpha 2(I) collagen expression in rat hepatic stellate cells overexpressing cytochrome P450 2E1. Role of H2O2 and cyclooxygenase-2. J Biol Chem 275(26):20136–20145

    Article  PubMed  CAS  Google Scholar 

  • Nieto N, Friedman SL, Cederbaum AI (2002a) Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem 277(12):9853–9864

    Article  PubMed  CAS  Google Scholar 

  • Nieto N, Friedman SL, Cederbaum AI (2002b) Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. Hepatology 35(1):62–73

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi K, Lieber CS (1977) Reconstitution of the microsomal ethanol-oxidizing system. Qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption. J Biol Chem 252(20):7124–7131

    PubMed  CAS  Google Scholar 

  • Oneta CM, Lieber CS, Li J, Rüttimann S, Schmid B, Lattmann J, Rosman AS, Seitz HK (2002) Dynamics of cytochrome P4502E1 activity in man: induction by ethanol and disappearance during withdrawal phase. J Hepatol 36(1):47–52

    Article  PubMed  CAS  Google Scholar 

  • Orellana M, Rodrigo R, Varela N, Araya J, Poniachik J, Csendes A, Smok G, Videla LA (2006) Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients. Hepatol Res 34(1):57–63

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, Clemens DL, Donohue TM Jr (2003) Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by ethanol. Biochem Pharmacol 66(5):697–710

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, Clemens DL, Donohue TM Jr (2005) Ethanol metabolism alters interferon gamma signaling in recombinant HepG2 cells. Hepatology 42(5):1109–1117

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, White RL, Todero S, McVicker BL, Thiele GM, Clemens DL, Tuma DJ, Donohue TM Jr (2007) Ethanol-induced oxidative stress suppresses generation of peptides for antigen presentation by hepatoma cells. Hepatology 45(1):53–61

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, White RL, Krutik VM, Wang T, Weinman SA, Donohue TM Jr (2008) Proteasome activation by hepatitis C core protein is reversed by ethanol-induced oxidative stress. Gastroenterology 134(7):2144–2152

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, White RL, Thiele GM, Donohue TM Jr (2009) Ethanol metabolism alters major histocompatibility complex class I-restricted antigen presentation in liver cells. Hepatology 49(4):1308–1315

    Article  PubMed  CAS  Google Scholar 

  • Osna NA, White RL, Donohue TM Jr, Beard MR, Tuma DJ, Kharbanda KK (2010) Impaired methylation as a novel mechanism for proteasome suppression in liver cells. Biochem Biophys Res Commun 391(2):1291–1296

    Article  PubMed  CAS  Google Scholar 

  • Otani K, Korenaga M, Beard MR, Li K, Qian T, Showalter LA, Singh AK, Wang T, Weinman SA (2005) Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells. Gastroenterology 128(1):96–107

    Article  PubMed  CAS  Google Scholar 

  • Pardini C, Vaglini F, Viaggi C, Caramelli A, Corsini GU (2008) Role of CYP2E1 in the mouse model of MPTP toxicity. Parkinsonism Relat Disord 14(Suppl 2):S119–S123

    Article  PubMed  Google Scholar 

  • Park KS, Sohn DH, Veech RL, Song BJ (1993) Translational activation of ethanol-inducible cytochrome P450 (CYP2E1) by isoniazid. Eur J Pharmacol 248(1):7–14

    PubMed  CAS  Google Scholar 

  • Qu W, Liu J, Dill AL, Saavedra JE, Keefer LK, Waalkes MP (2009) V-PROLI/NO, a nitric oxide donor prodrug, protects liver cells from arsenic-induced toxicity. Cancer Sci 100(3):382–388

    Article  PubMed  CAS  Google Scholar 

  • Ramaiah SK, Apte U, Mehendale HM (2001) Cytochrome P4502E1 induction increases thioacetamide liver injury in diet-restricted rats. Drug Metab Dispos 29(8):1088–1095

    PubMed  CAS  Google Scholar 

  • Raucy JL, Schultz ED, Wester MR, Arora S, Johnston DE, Omdahl JL, Carpenter SP (1997) Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity. Drug Metab Dispos 25(12):1429–1435

    PubMed  CAS  Google Scholar 

  • Raucy JL, Lasker J, Ozaki K, Zoleta V (2004) Regulation of CYP2E1 by ethanol and palmitic acid and CYP4A11 by clofibrate in primary cultures of human hepatocytes. Toxicol Sci 79(2):233–241

    Article  PubMed  CAS  Google Scholar 

  • Raza H, Prabu SK, Robin MA, Avadhani NG (2004) Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress. Diabetes 53(1):185–194

    Article  PubMed  CAS  Google Scholar 

  • Reed DJ (2004) Mitochondrial glutathione and chemically induced stress including ethanol. Drug Metab Rev 36(3–4):569–582

    Article  PubMed  CAS  Google Scholar 

  • Rigamonti C, Vidali M, Donato MF, Sutti S, Occhino G, Ivaldi A, Arosio E, Agnelli F, Rossi G, Colombo M, Albano E (2009) Serum autoantibodies against cytochrome P450 2E1 (CYP2E1) predict severity of necroinflammation of recurrent hepatitis C. Am J Transplant 9(3):601–609

    Article  PubMed  CAS  Google Scholar 

  • Roberts BJ, Shoaf SE, Jeong KS, Song BJ (1994) Induction of CYP2E1 in liver, kidney, brain and intestine during chronic ethanol administration and withdrawal: evidence that CYP2E1 possesses a rapid phase half-life of 6 h or less. Biochem Biophys Res Commun 205(2):1064–1071

    Article  PubMed  CAS  Google Scholar 

  • Roberts BJ, Shoaf SE, Song BJ (1995) Rapid changes in cytochrome P4502E1 (CYP2E1) activity and other P450 isozymes following ethanol withdrawal in rats. Biochem Pharmacol 49(11):1665–1673

    Article  PubMed  CAS  Google Scholar 

  • Robin MA, Anandatheerthavarada HK, Fang JK, Cudic M, Otvos L, Avadhani NG (2001) Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N terminus and requires mitochondrial specific electron transfer proteins for activity. J Biol Chem 276(27):24680–24689

    Article  PubMed  CAS  Google Scholar 

  • Robin MA, Sauvage I, Grandperret T, Descatoire V, Pessayre D, Fromenty B (2005) Ethanol increases mitochondrial cytochrome P450 2E1 in mouse liver and rat hepatocytes. FEBS Lett 579(30):6895–6902

    Article  PubMed  CAS  Google Scholar 

  • Roede JR, Stewart BJ, Petersen DR (2008) Decreased expression of peroxiredoxin 6 in a mouse model of ethanol consumption. Free Radic Biol Med 45(11):1551–1558

    Article  PubMed  CAS  Google Scholar 

  • Ronis MJ, Johansson I, Hultenby K, Lagercrantz J, Glaumann H, Ingelman-Sundberg M (1991) Acetone-regulated synthesis and degradation of cytochrome P450E1 and cytochrome P4502B1 in rat liver [corrected]. Eur J Biochem 198(2):383–389, Erratum in Eur J Biochem 200(3):812

    Article  PubMed  CAS  Google Scholar 

  • Ronis MJ, Korourian S, Blackburn ML, Badeaux J, Badger TM (2010) The role of ethanol metabolism in development of alcoholic steatohepatitis in the rat. Alcohol 44(2):157–169

    Article  PubMed  CAS  Google Scholar 

  • Rowlands JC, He L, Badger TM (2003) Glucose inhibition of the induction of CYP2E1 mRNA expression by ethanol in FGC-4 cells. Xenobiotica 33(4):389–397

    Article  PubMed  CAS  Google Scholar 

  • Runge-Morris M, Feng Y, Zangar RC, Novak RF (1996) Effects of hydrazine, phenelzine, and hydralazine treatment on rat hepatic and renal drug-metabolizing enzyme expression. Drug Metab Dispos 24(7):734–737

    PubMed  CAS  Google Scholar 

  • Ruwali M, Khan AJ, Shah PP, Singh AP, Pant MC, Parmar D (2009) Cytochrome P450 2E1 and head and neck cancer: interaction with genetic and environmental risk factors. Environ Mol Mutagen 50(6):473–482

    Article  PubMed  CAS  Google Scholar 

  • Salmela KS, Kessova IG, Tsyrlov IB, Lieber CS (1998) Respective roles of human cytochrome P-4502E1, 1A2, and 3A4 in the hepatic microsomal ethanol oxidizing system. Alcohol Clin Exp Res 22(9):2125–2132

    Article  PubMed  CAS  Google Scholar 

  • Sampey BP, Korourian S, Ronis MJ, Badger TM, Petersen DR (2003) Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury. Alcohol Clin Exp Res 27(6):1015–1022

    Article  PubMed  CAS  Google Scholar 

  • Schattenberg JM, Wang Y, Rigoli RM, Koop DR, Czaja MJ (2004) CYP2E1 overexpression alters hepatocyte death from menadione and fatty acids by activation of ERK1/2 signaling. Hepatology 39(2):444–455

    Article  PubMed  CAS  Google Scholar 

  • Schattenberg JM, Wang Y, Singh R, Rigoli RM, Czaja MJ (2005) Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling. J Biol Chem 280(11):9887–9894

    Article  PubMed  CAS  Google Scholar 

  • Sewer MB, Morgan ET (1998) Down-regulation of the expression of three major rat liver cytochrome P450S by endotoxin in vivo occurs independently of nitric oxide production. J Pharmacol Exp Ther 287(1):352–358

    PubMed  CAS  Google Scholar 

  • Sewer MB, Barclay TB, Morgan ET (1998) Down-regulation of cytochrome P450 mRNAs and proteins in mice lacking a functional NOS2 gene. Mol Pharmacol 54(2):273–279

    PubMed  CAS  Google Scholar 

  • Shankar K, Liu X, Singhal R, Chen JR, Nagarajan S, Badger TM, Ronis MJ (2008) Chronic ethanol consumption leads to disruption of vitamin D3 homeostasis associated with induction of renal 1,25 dihydroxyvitamin D3-24-hydroxylase (CYP24A1). Endocrinology 149(4):1748–1756

    Article  PubMed  CAS  Google Scholar 

  • Shimizu M, Lasker JM, Tsutsumi M, Lieber CS (1990) Immunohistochemical localization of ethanol-inducible P450IIE1 in the rat alimentary tract. Gastroenterology 99(4):1044–1053

    PubMed  CAS  Google Scholar 

  • Sidhu JS, Liu F, Boyle SM, Omiecinski CJ (2001) PI3K inhibitors reverse the suppressive actions of insulin on CYP2E1 expression by activating stress-response pathways in primary rat hepatocytes. Mol Pharmacol 59(5):1138–1146

    PubMed  CAS  Google Scholar 

  • Simi A, Ingelman-Sundberg M (1999) Post-translational inhibition of cytochrome P-450 2E1 expression by chlomethiazole in Fao hepatoma cells. J Pharmacol Exp Ther 289(2):847–852

    PubMed  CAS  Google Scholar 

  • Sindhu RK, Koo JR, Sindhu KK, Ehdaie A, Farmand F, Roberts CK (2006) Differential regulation of hepatic cytochrome P450 monooxygenases in streptozotocin-induced diabetic rats. Free Radic Res 40(9):921–928

    Article  PubMed  CAS  Google Scholar 

  • Singh M, Khan AJ, Shah PP, Shukla R, Khanna VK, Parmar D (2008) Polymorphism in environment responsive genes and association with Parkinson disease. Mol Cell Biochem 312(1–2):131–138

    Article  PubMed  CAS  Google Scholar 

  • Singh R, Wang Y, Schattenberg JM, Xiang Y, Czaja MJ (2009) Chronic oxidative stress sensitizes hepatocytes to death from 4-hydroxynonenal by JNK/c-Jun overactivation. Am J Physiol Gastrointest Liver Physiol 297(5):G907–G917

    Article  PubMed  CAS  Google Scholar 

  • Soh Y, Rhee HM, Sohn DH, Song BJ (1996) Immunological detection of CYP2E1 in fresh rat lymphocytes and its pretranslational induction by fasting. Biochem Biophys Res Commun 227(2):541–546

    Article  PubMed  CAS  Google Scholar 

  • Song BJ, Gelboin HV, Park SS, Yang CS, Gonzalez FJ (1986) Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem 261(35):16689–16697

    PubMed  CAS  Google Scholar 

  • Song BJ, Veech RL, Saenger P (1990) Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin-dependent diabetics. J Clin Endocrinol Metab 71(4):1036–1040

    Article  PubMed  CAS  Google Scholar 

  • Starkel P, Laurent S, Petit M, Van Den Berge V, Lambotte L, Horsmans Y (2000) Early down-regulation of cytochrome P450 3A and 2E1 in the regenerating rat liver is not related to the loss of liver mass or the process of cellular proliferation. Liver 20(5):405–410

    Article  PubMed  CAS  Google Scholar 

  • Sumner SC, Fennell TR, Moore TA, Chanas B, Gonzalez F, Ghanayem BI (1999) Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice. Chem Res Toxicol 12(11):1110–1116

    Article  PubMed  CAS  Google Scholar 

  • Sutti S, Vidali M, Mombello C, Sartori M, Ingelman-Sundberg M, Albano E (2010a) Breaking self-tolerance toward cytochrome P4502E1 (CYP2E1) in chronic hepatitis C: possible role for molecular mimicry. J Hepatol 53(3):431–438

    Article  PubMed  CAS  Google Scholar 

  • Sutti S, Vidali M, Mombello C, Sartori M, Albano E (2010b) Conformational anti-cytochrome P4502E1 (CYP2E1) auto-antibodies contribute to necro-inflammatory injury in chronic hepatitis C. J Viral Hepat 17(10):685–690

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H, Johansson I, French SW, Ingelman-Sundberg M (1992) Effects of dietary fat composition on activities of the microsomal ethanol oxidizing system and ethanol-inducible cytochrome P450 (CYP2E1) in the liver of rats chronically fed ethanol. Pharmacol Toxicol 70(5 Pt 1):347–351

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Lasker JM, Rosman AS, Lieber CS (1993) Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA. Hepatology 17(2):236–245

    PubMed  CAS  Google Scholar 

  • Terelius Y, Norsten-Höög C, Cronholm T, Ingelman-Sundberg M (1991) Acetaldehyde as a substrate for ethanol-inducible cytochrome P450 (CYP2E1). Biochem Biophys Res Commun 179(1):689–694

    Article  PubMed  CAS  Google Scholar 

  • Teschke R, Hasumura Y, Joly JG, Lieber CS (1972) Microsomal ethanol-oxidizing system (MEOS): purification and properties of a rat liver system free of catalase and alcohol dehydrogenase. Biochem Biophys Res Commun 49(5):1187–1193

    Article  PubMed  CAS  Google Scholar 

  • Teschke R, Hasumura Y, Lieber CS (1974) Hepatic microsomal ethanol-oxidizing system: solubilization, isolation, and characterization. Arch Biochem Biophys 163(1):404–415

    Article  PubMed  CAS  Google Scholar 

  • Tierney DJ, Haas AL, Koop DR (1992) Degradation of cytochrome P450 2E1: selective loss after labilization of the enzyme. Arch Biochem Biophys 293(1):9–16

    Article  PubMed  CAS  Google Scholar 

  • Tindberg N, Ingelman-Sundberg M (1996) Expression, catalytic activity, and inducibility of cytochrome P450 2E1 (CYP2E1) in the rat central nervous system. J Neurochem 67(5):2066–2073

    Article  PubMed  CAS  Google Scholar 

  • Tindberg N, Baldwin HA, Cross AJ, Ingelman-Sundberg M (1996) Induction of cytochrome P450 2E1 expression in rat and gerbil astrocytes by inflammatory factors and ischemic injury. Mol Pharmacol 50(5):1065–1072

    PubMed  CAS  Google Scholar 

  • Trafalis DT, Panteli ES, Grivas A, Tsigris C, Karamanakos PN (2010) CYP2E1 and risk of chemically mediated cancers. Expert Opin Drug Metab Toxicol 6(3):307–319

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi M, Lasker JM, Takahashi T, Lieber CS (1993) In vivo induction of hepatic P4502E1 by ethanol: role of increased enzyme synthesis. Arch Biochem Biophys 304(1):209–218

    Article  PubMed  CAS  Google Scholar 

  • Tumer TB, Yilmaz D, Tanrikut C, Sahin G, Ulusoy G, Arinç E (2010) DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia. Leuk Res 34(10):1275–1281

    Article  PubMed  CAS  Google Scholar 

  • Ulusoy G, Adali O, Tumer TB, Sahin G, Gozdasoglu S, Arinç E (2007) Significance of genetic polymorphisms at multiple loci of CYP2E1 in the risk of development of childhood acute lymphoblastic leukemia. Oncology 72(1–2):125–131

    Article  PubMed  CAS  Google Scholar 

  • Upadhya SC, Tirumalai PS, Boyd MR, Mori T, Ravindranath V (2000) Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization. Arch Biochem Biophys 373(1):23–34

    Article  PubMed  CAS  Google Scholar 

  • Vaglini F, Pardini C, Viaggi C, Bartoli C, Dinucci D, Corsini GU (2004) Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease. J Neurochem 91(2):285–298

    Article  PubMed  CAS  Google Scholar 

  • Varela NM, Quiñones LA, Orellana M, Poniachik J, Csendes A, Smok G, Rodrigo R, Cáceres DD, Videla LA (2008) Study of cytochrome P450 2E1 and its allele variants in liver injury of nondiabetic, nonalcoholic steatohepatitis obese women. Biol Res 41(1):81–92

    Article  PubMed  Google Scholar 

  • Vasiliou V, Ziegler TL, Bludeau P, Petersen DR, Gonzalez FJ, Deitrich RA (2006) CYP2E1 and catalase influence ethanol sensitivity in the central nervous system. Pharmacogenet Genomics 16(1):51–58

    Article  PubMed  CAS  Google Scholar 

  • Veeramachaneni S, Ausman LM, Choi SW, Russell RM, Wang XD (2008) High dose lycopene supplementation increases hepatic cytochrome P4502E1 protein and inflammation in alcohol-fed rats. J Nutr 138(7):1329–1335

    PubMed  CAS  Google Scholar 

  • Viaggi C, Vaglini F, Pardini C, Caramelli A, Corsini GU (2009) MPTP-induced model of Parkinson’s disease in cytochrome P450 2E1 knockout mice. Neuropharmacology 56(8):1075–1081

    Article  PubMed  CAS  Google Scholar 

  • Vidali M, Occhino G, Ivaldi A, Serino R, Moia S, Alchera E, Carini R, Rigamonti C, Sartori M, Albano E (2007) Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic hepatitis C. J Hepatol 46(4):605–612

    Article  PubMed  CAS  Google Scholar 

  • Videla LA, Rodrigo R, Orellana M, Fernandez V, Tapia G, Quiñones L, Varela N, Contreras J, Lazarte R, Csendes A, Rojas J, Maluenda F, Burdiles P, Diaz JC, Smok G, Thielemann L, Poniachik J (2004) Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci (Lond) 106(3):261–268

    Article  CAS  Google Scholar 

  • Wan YJ, Morimoto M, Thurman RG, Bojes HK, French SW (1995) Expression of the peroxisome proliferator-activated receptor gene is decreased in experimental alcoholic liver disease. Life Sci 56(5):307–317

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Shankar K, Ronis MJ, Mehendale HM (2000) Potentiation of thioacetamide liver injury in diabetic rats is due to induced CYP2E1. J Pharmacol Exp Ther 294(2):473–479

    PubMed  CAS  Google Scholar 

  • Wang H, Chanas B, Ghanayem BI (2002a) Effect of methacrylonitrile on cytochrome P-450 2E1 (CYP2E1) expression in male F344 rats. J Toxicol Environ Health A65(7):523–537

    Article  Google Scholar 

  • Wang H, Chanas B, Ghanayem BI (2002b) Cytochrome P450 2E1 (CYP2E1) is essential for acrylonitrile metabolism to cyanide: comparative studies using CYP2E1-null and wild-type mice. Drug Metab Dispos 30(8):911–917

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Ausman LM, Russell RM, Greenberg AS, Wang XD (2008) Increased apoptosis in high-fat diet-induced nonalcoholic steatohepatitis in rats is associated with c-Jun NH2-terminal kinase activation and elevated proapoptotic Bax. J Nutr 138(10):1866–1871

    PubMed  CAS  Google Scholar 

  • Wang Y, Millonig G, Nair J, Patsenker E, Stickel F, Mueller S, Bartsch H, Seitz HK (2009) Ethanol-induced cytochrome P4502E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease. Hepatology 50(2):453–461

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Guan S, Acharya P, Koop DR, Liu Y, Liao M, Burlingame AL, Correia MA (2011) Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1: identification of sites targeted for phosphorylation and ubiquitination. J Biol Chem 286(11):9443–9456

    Article  PubMed  CAS  Google Scholar 

  • Woodcroft KJ, Novak RF (1997) Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes. Chem Biol Interact 107(1–2):75–91

    Article  PubMed  CAS  Google Scholar 

  • Woodcroft KJ, Novak RF (1999) The role of phosphatidylinositol 3-kinase, Src kinase, and protein kinase A signaling pathways in insulin and glucagon regulation of CYP2E1 expression. Biochem Biophys Res Commun 266(2):304–307

    Article  PubMed  CAS  Google Scholar 

  • Woodcroft KJ, Hafner MS, Novak RF (2002) Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 35(2):263–273

    Article  PubMed  CAS  Google Scholar 

  • Wrighton SA, Thomas PE, Molowa DT, Haniu M, Shively JE, Maines SL, Watkins PB, Parker G, Mendez-Picon G, Levin W et al (1986) Characterization of ethanol-inducible human liver N-nitrosodimethylaminedemethylase. Biochemistry 25(22):6731–6735

    Article  PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (1993a) Combined effects of streptozotocin-induced diabetes plus 4-methylpyrazole treatment on rat liver cytochrome P4502E1. Arch Biochem Biophys 302(1):175–182

    Article  PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (1993b) Ethanol consumption by the nursing mother induces cytochrome P-4502E1 in neonatal rat liver. J Pharmacol Exp Ther 267(1):560–566

    PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (1994) Characterization of pyrazole and 4-methylpyrazole induction of cytochrome P4502E1 in rat kidney. J Pharmacol Exp Ther 270(1):407–413

    PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (1996) Ethanol cytotoxicity to a transfected HepG2 cell line expressing human cytochrome P4502E1. J Biol Chem 271(39):23914–23919

    Article  PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (2000) Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1. Mol Cell Biochem 204(1–2):157–167

    Article  PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (2001) Sodium salicylate increases CYP2E1 levels and enhances arachidonic acid toxicity in HepG2 cells and cultured rat hepatocytes. Mol Pharmacol 59(4):795–805

    PubMed  CAS  Google Scholar 

  • Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27:277–284

    PubMed  Google Scholar 

  • Wu D, Cederbaum AI (2005) Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1. Toxicol Appl Pharmacol 207(Suppl 2):70–76

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Leo MA, Lieber CS (2003a) Lycopene attenuates arachidonic acid toxicity in HepG2 cells overexpressing CYP2E1. Biochem Biophys Res Commun 303(3):745–750

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Leo MA, Lieber CS (2003b) Lycopene attenuates alcoholic apoptosis in HepG2 cells expressing CYP2E1. Biochem Biophys Res Commun 308(3):614–618

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Leo MA, Lieber CS (2005) DLPC attenuates alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1. Alcohol Alcohol 40(3):172–175

    Article  PubMed  Google Scholar 

  • Yadav S, Dhawan A, Singh RL, Seth PK, Parmar D (2006) Expression of constitutive and inducible cytochrome P450 2E1 in rat brain. Mol Cell Biochem 286(1–2):171–180

    Article  PubMed  CAS  Google Scholar 

  • Yano H, Tsutsumi M, Fukura M, Chen WB, Shimanaka K, Tsuchishima M, Takase S, Imaoka S, Funae Y (2001) Study of cytochrome P4502E1 mRNA level of mononuclear cells in patients with alcoholic liver disease. Alcohol Clin Exp Res 25(Suppl 6):2S–6S

    Article  PubMed  CAS  Google Scholar 

  • Yue J, Khokhar J, Miksys S, Tyndale RF (2009) Differential induction of ethanol-metabolizing CYP2E1 and nicotine-metabolizing CYP2B1/2 in rat liver by chronic nicotine treatment and voluntary ethanol intake. Eur J Pharmacol 609(1–3):88–95

    Article  PubMed  CAS  Google Scholar 

  • Zaluzny L, Farrell GC, Murray M (1990) Effect of genetic obesity and experimental diabetes on hepatic microsomal mixed function oxidase activities. J Gastroenterol Hepatol 5(3):256–263

    Article  PubMed  CAS  Google Scholar 

  • Zangar RC, Woodcroft KJ, Kocarek TA, Novak RF (1995) Xenobiotic-enhanced expression of cytochrome P450 2E1 and 2B1/2B2 in primary cultured rat hepatocytes. Drug Metab Dispos 23(7):681–687

    PubMed  CAS  Google Scholar 

  • Zhukov A, Ingelman-Sundberg M (1997) Selective fast degradation of cytochrome P-450 2E1 in serum-deprived hepatoma cells by a mechanism sensitive to inhibitors of vesicular transport. Eur J Biochem 247(1):37–43

    Article  PubMed  CAS  Google Scholar 

  • Zhukov A, Ingelman-Sundberg M (1999) Relationship between cytochrome P450 catalytic cycling and stability: fast degradation of ethanol-inducible cytochrome P450 2E1 (CYP2E1) in hepatoma cells is abolished by inactivation of its electron donor NADPH-cytochrome P450 reductase. Biochem J 340(Pt 2):453–458

    Article  PubMed  CAS  Google Scholar 

  • Zhukov A, Werlinder V, Ingelman-Sundberg M (1993) Purification and characterization of two membrane bound serine proteinases from rat liver microsomes active in degradation of cytochrome P450. Biochem Biophys Res Commun 197(1):221–228

    Article  PubMed  CAS  Google Scholar 

  • Zimatkin SM, Pronko SP, Vasiliou V, Gonzalez FJ, Deitrich RA (2006) Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol Clin Exp Res 30(9):1500–1505

    Article  PubMed  CAS  Google Scholar 

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    Aparajita Dey Ph.D.

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Dey, A. (2013). Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario. In: Dey, A. (eds) Cytochrome P450 2E1: Its Role in Disease and Drug Metabolism. Subcellular Biochemistry, vol 67. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5881-0_1

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