Skip to main content
SpringerLink
Log in

CYP2E1 – Biochemical and Toxicological Aspects and Role in Alcohol-Induced Liver Injury

  • Chapter
  • First Online:
Advances in Bioactivation Research

Part of the book series: Biotechnology: Pharmaceutical Aspects ((PHARMASP,volume IX))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adachi, M., and Ishii, H. 2002. Role of mitochondria in alcoholic liver injury. Free Rad. Biol. Med. 32:487–491.

    Article  PubMed  CAS  Google Scholar 

  • Albano, E., Tomasi A., Goria-Gatti, L., Poli G., Vannini A., and Dianzani M. U. 1987. Free radical metabolism of alcohols in rat liver microsomes. Free Rad. Res. Commun. 3:243–253.

    Article  CAS  Google Scholar 

  • Albano, E., Tomasi, A., Persson, J. O., Terelius, Y., Goria-Gatti, L., Ingelman-Sundberg, M., and Dianzani, M. U. 1991. Role of ethanol-inducible cytochrome P-450 (P-450IIE1) in catalysis of the free radical activation of aliphatic alcohols. Biochem. Pharmacol. 41:1895–1902.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Aleynik, M. K., Leo, M. A., Aleynik, S. I., and Lieber, C. S. 1999. Polyenylphosphatidyl-choline opposes the increase of cytochrome P4502E1 by ethanol and corrects its iron-induced decrease. Alcoholism: Clin. Exp. Res. 23:96–100.

    Article  CAS  Google Scholar 

  • Arteel, G. E. 2003. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenerology 124:778–790.

    Article  CAS  Google Scholar 

  • Asai, H., Imaoka, S., Kuroki, T., Monna, T., and Funae, Y. 1996. Microsomal ethanol oxidizing system activity by human hepatic cytochrome P-450s. J. Pharmacol. Exp. Ther. 277:1004–1009.

    PubMed  CAS  Google Scholar 

  • Badger, D. A., Kuester, R. K., Sauer, J. M., and Sipes, L. G. 1997. Gadolinium chloride reduces cytochrome p450: relevance to chemical induced hepatotoxicity. Toxicology 121:143–153.

    Article  PubMed  CAS  Google Scholar 

  • Badger, T. M.., Korourian, S., Hakkak, R., Ronnis, M. J. J., Ingelman- Sundberg, M., Shelnutt, S. R., and Waldron, J. 1998. Carbohydrate deficiency as a possible factor in ethanol-induced hepatic necrosis. Alcohol. Clin. Exp. Res. 22:742.

    Article  Google Scholar 

  • Badger, T. M., Ronis, M. J. J., Seitz, H. K., Albano, E., Ingelman-Sundberg, M., and Lieber, C. S. 2003. Alcohol metabolism: role in toxicity and carcinogenicity. Alcohol. Clin. Exp. Res. 27:336–347.

    Article  PubMed  Google Scholar 

  • Bai, J. X., and Cederbaum, A. I. 2001. Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells. J. Biol. Chem. 276:4315–4321.

    Article  PubMed  CAS  Google Scholar 

  • Bai, J. X., and Cederbaum, A. I. 2004. Adenovirus-mediated overexpression of CYP2E1 increases sensitivity of HepG2 cells to acetaminophen induced cytotoxicity. Mol. Cell. Biochem. 262:165–176.

    Article  PubMed  CAS  Google Scholar 

  • Bai, J. X., and Cederbaum, A. I. 2006. Adenovirus-mediated expression of CYP2E1 produces liver toxicity in mice. Toxicol. Sci. 91:365–371.

    Article  PubMed  CAS  Google Scholar 

  • Bailey, S. M., and Cunningham, C. C. 2002. Contribution of mitochondria to oxidative stress associated with alcoholic liver disease. Free Rad. Biol. Med. 32:11–16.

    Article  PubMed  CAS  Google Scholar 

  • Barcelo, S., Gardiner, J. M., Gescher, A., and Chipman, J. K. 1996. CYP2E1-mediated mechanism of antigenotoxicity of the broccoli constituent sulforaphane. Carcinogenesis 17:277–282.

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce, F., Yuan, Q. X., Li, J., French, B. A., Fang, C., Ingelman- Sundberg, M., and French, S. W. 2000. The effect of ethanol-induced cytochrome P450 2E1 on the inhibition of proteasome activity by alcohol. Biochem. Biophys. Res. Commun. 279:23–29.

    Article  PubMed  CAS  Google Scholar 

  • Bardag-Gorce, F., Li, J., French, B. A., and French, S. W. 2002. Ethanol withdrawal induced CYP2E1 degradation in vivo, blocked by the proteasomal inhibitor PS-341. Free Rad. Biol. Med. 32:17–21.

    Article  PubMed  CAS  Google Scholar 

  • Bellward, G. D., Chang, T., Rodrigues, J. H., McNeil J. H., Maines, S., Ryan, D. E., Levin, W., and Thomas, P. E., 1987. Hepatic cytochrome P-450 j induction in the spontaneously diabetic BB rat. Mol. Pharmacol. 33:140–143.

    Google Scholar 

  • Blanck, J., Ristau, O., Zhukov, A. A., Archakov, A. L., Rein, H., and Ruckpaul, K. 1991. Cytochrome P450 spin state and leakiness of the monooxygenase pathway. Xenobiotica 21:121–135.

    Article  PubMed  CAS  Google Scholar 

  • Bolt, M., Koos, P. H., and Their, R., 2003. The cytochrome P450 isoenzyme CYP2E1 in the biological processing of industrial chemicals. Int. Arch. Occup. Environ. Health 76:174–185.

    PubMed  CAS  Google Scholar 

  • Bondoc, F. Y., Bao, Z., Hu, W. Y., Gonzalez, F. J., Wang, Y., Yang, C. S., and Hong, J. Y. 1999. Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice. Biochem. Pharmacol. 58:461–463.

    Article  PubMed  CAS  Google Scholar 

  • Bondy, S. C. 1992. Ethanol toxicity and oxidative stress. Toxicol. Lett. 63:231–242.

    Article  PubMed  CAS  Google Scholar 

  • Bourdi, M., Chen, W., Peter, R. M., Martin, J. L., Buters, J. T., Nelson, S. D., and Pohl, L. R. 1996. Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem. Res. Toxicol. 9:1159–1166.

    Article  PubMed  CAS  Google Scholar 

  • Carlson, G. P. 2004. Comparison of the susceptibility of wild type and CYP2E1 knockout mice to the hepatotoxic and neurotoxic effects of styrene and styrene oxide. Toxicol. Lett. 150:335–339.

    Article  PubMed  CAS  Google Scholar 

  • Caro, A. A., and Cederbaum, A. I. 2001. Synergistic toxicity of iron and arachidonic acid in HepG2 cells overexpressing CYP2E1. Mol. Pharmacol. 60:742–752.

    PubMed  CAS  Google Scholar 

  • Caro, A. A., and Cederbaum, A. I. 2002. Role of calcium and calcium-activated proteases in CYP2E1-dependent toxicity in HepG2 cells. J. Biol. Chem. 277:104–113.

    Article  PubMed  CAS  Google Scholar 

  • Caro, A. A., and Cederbaum, A. I. 2005. Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem. Pharmacol. 69:1081–1093.

    Article  PubMed  CAS  Google Scholar 

  • Castillo, T., Koop, D. R., Kamimura, S., Triadafilopoulos, G., and Tsukamoto, H. 1992. Role of cytochrome P4502E1 in ethanol, carbon tetrachloride and iron-dependent microsomal lipid peroxidation. Hepatology 16:992–996.

    Article  PubMed  CAS  Google Scholar 

  • Cederbaum, A. I. 2001. Introduction serial review: alcohol, oxidative stress and cell injury. Free Rad. Biol. Med. 31:1524–1526.

    Article  PubMed  CAS  Google Scholar 

  • Chance, B., Sies, H., and Boveris, A. 1979. Hydroperoxide metabolism in mammalian organisms. Physiol. Rev. 59:527–604.

    PubMed  CAS  Google Scholar 

  • Chen, Q., and Cederbaum, A. I. 1998. Cytotoxicity and apoptosis produced by cytochrome P4502E1 in HepG2 cells. Mol. Pharmacol. 53:638–648.

    PubMed  CAS  Google Scholar 

  • Chen, Q., Galleano, M., and Cederbaum, A. I. 1997. Cytotoxicity and apoptosis produced by arachidonic acid in HepG2 cells over-expressing human cytochrome P4502E1. J. Biol. Chem. 272:14532–14541.

    Article  PubMed  CAS  Google Scholar 

  • Cheung, C., Yu A. M., Ward, J. M., Krausz, K. W., Akiyama, T. E., Feigenbaum, L., and Gonzalez, F. J. 2005. The CYP2E1 humanized transgenic mouse; role of CYP2E1 in acetaminophen toxicity. Drug Metab. Disp. 33: 449–457.

    Article  CAS  Google Scholar 

  • Choi, E. Y., Kim, S. G., Lee, J. W., Yoo, J. K., Shin, J. K., and Kim, N. D. 1996. Suppression of rat hepatic cytochrome P4502E1 expression by YH439, an experiment hepatoprotectant: protective role against hepatic injury. Biochem. Pharmacol. 52:1219–1225.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Dai, Y., and Cederbaum, A. I. 1995a. Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J. Pharmacol. Exp. Ther. 273:1497–1505.

    CAS  Google Scholar 

  • Dai, Y., and Cederbaum, A. I. 1995b. Inactivation and degradation of human cytochrome P4502E1 by CC14 in a transfected HepG2 cell line. J. Pharmacol. Exp. Ther. 275:1614–1622.

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • De Groot, H. 1994. Reactive oxygen species in tissue injury. Hepatogastroenterology 41:328–332.

    PubMed  Google Scholar 

  • DeWaziers, I., Garlatti, M., Bouguet, J., Beaune, P. H., and Barouki, R. 1995. Insulin down-regulates cytochrome P-450 2B and 2E expression at the posttranscriptional level in the rat hepatoma cell line. Mol. Pharmacol. 47:474–479.

    CAS  Google Scholar 

  • Dicker, E., and Cederbaum, A. I. 1987. Hydroxyl radical generation by microsomes after chronic ethanol consumption. Alcohol. Clin. Exp. Res. 11:309–314.

    Article  PubMed  CAS  Google Scholar 

  • Dicker, E., and Cederbaum, A. I. 1988. Increased oxygen radical dependent inactivation of metabolic enzymes by liver microsomes after chronic ethanol consumption. FASEB J. 2:2901–2906.

    PubMed  CAS  Google Scholar 

  • Donohue, T. M., Zetterman, R. K., Zhang-Gouilon, Z. Q., and French, S. W. 1998. Peptidase activities of the multicatalytic protease in rat liver after voluntary and intragastric ethanol administration. Hepatology 28:486–491.

    Article  PubMed  CAS  Google Scholar 

  • Ekstrom G., and 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: 1313–1319.

    Article  PubMed  CAS  Google Scholar 

  • Eliasson, E., and Kenna, J. G. 1996. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol. Pharmacol. 50:573–582.

    PubMed  CAS  Google Scholar 

  • Eliasson, E., Johansson, I., and Ingelman-Sundberg, M. 1988. Ligand-dependent maintenance of ethanol-inducible cytochrome P450 in primary hepatocyte cell culture. Biochem. Biophys. Res. Commun. 150:436–443.

    Article  PubMed  CAS  Google Scholar 

  • Eliasson, E., Johansson, I., and Ingelman-Sundberg, M. 1990. Substrate-hormone, and cAMP-regulated cytochrome P450 degradation. Proc. Natl. Acad. Sci. U.S.A. 87:3225–3229.

    Google Scholar 

  • Eliasson, E., Mkrtachian, S., and 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. 267:15765–15769.

    PubMed  CAS  Google Scholar 

  • Fataccioli, V., Andraud, E., Gentil, M., French, S. W., and Rouach, H. 1999. Effects of chronic ethanol administration on rat liver proteasome activities: relationship with oxidative stress. Hepatology 29:14–20.

    Article  PubMed  CAS  Google Scholar 

  • French, S. W., Morimoto, M., Reitz, R. C., Koop, D., Klopfenstein, B., Estes, K., Clot, P., Ingelman-Sundberg, M., and Albano, E. 1997. Lipid peroxidation, CYP2E1 and arachidonic acid metabolism in alcoholic liver disease in rats. J. Nutr. 127:907S–911S.

    PubMed  CAS  Google Scholar 

  • Girre, C., Lucas, D., Hispard, F. R., Menez, C., Dally, S., and Menez, J. P. 1994. Assessment of cytochrome P4502E1 in induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem. Pharmacol. 47:1503–1508.

    Article  PubMed  CAS  Google Scholar 

  • Gong, P., Cederbaum, A. I., and Nieto, N. 2003. Increased expression of cytochrome P4502E1 induces heme oxygenase 1 through ERK MAPK pathway. J. Biol. Chem. 278:29693–29700.

    Article  PubMed  CAS  Google Scholar 

  • Gong P., Hu, B., and Cederbaum, A. I. 2004. Diallyl sulfide induces heme oxygenase 1 through MAPK pathway. Arch. Biochem. Biophys. 432:252–260.

    Article  PubMed  CAS  Google Scholar 

  • Gorsky, L. D., Koop, D. R., and Coon, M. J. 1984. On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P450. J. Biol. Chem. 259:6812–6817.

    PubMed  CAS  Google Scholar 

  • Gouillon, Z., Lucas, D., Li, J., Hagbjork, A. L., French, B. A., Fu, P., Fang, C., Ingelman-Sundberg, M., Donohue, T. M. Jr., and French, S. W. 2000. Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole. Proc. Soc. Exp. Biol. Med. 224:302–308.

    Google Scholar 

  • Guengerich, F. P. 1987. Mammalian cytochrome P450. Boca Raton, FL: CRC Press.

    Google Scholar 

  • Guengerich, F. P. 2001. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14:611–650.

    Article  PubMed  CAS  Google Scholar 

  • Halliwell, B. 1999. Antioxidant defense mechanisms: from the beginning to the end. Free Rad. Res. 31:261–272.

    Article  CAS  Google Scholar 

  • Hansson, T., Tindberg, N., Ingelman-Sundberg, M., and Kohler, C. 1990. Regional distribution of ethanol-inducible cytochrome P-450 IIE1 in the rat brain. Neuroscience 34:451–463.

    Article  PubMed  CAS  Google Scholar 

  • Harada, S., Agarwal D. P., Nomura, F., and Higuchi, S. 2001. Metabolic and ethnic determinants of alcohol-related drinking habits and vulnerability to alcohol-related disorder. Alcohol. Clin. Exp. Res. 25:71S–75S.

    Article  PubMed  CAS  Google Scholar 

  • He, K., Iyer, K. R., Hayes, R. N., Sinz, M. W., Woolf, T. F., and Hollenberg, P. F. 1998. Inactivation of cytochrome P4503A4 by bergamottin, a component of grapefruit juice. Chem. Res. Toxicol. 11:252–259.

    Article  PubMed  CAS  Google Scholar 

  • Hoivik, D. J., Manautou, J. E., Tveit, A., Hart., S. G., Khairallah, E. A., and Cohen S. D. 1995. Gender-related differences in susceptibility to acetaminophen induced protein arylation and nephrotocicity in the CD-1 mouse. Toxicol Appl. Pharmacol. 130:257–271.

    Article  PubMed  CAS  Google Scholar 

  • Hong, J. Y., Pan, J., Gonzalez, F. J., Gelboin, H. V., and Yang, C. S. 1987. The induction of a specific form of cytochrome P-450 (P-450 j) by fasting. Biochem. Biophys. Res. Commun. 142:1077–1083.

    Article  PubMed  CAS  Google Scholar 

  • Hong, J. Y., Ning, S. M., Ma, B. L., Lee, M. J., Pan, J. M., and Yang C. S. 1990. Roles of pituitary hormones in the regulation of hepatic cytochrome P-450IIE1 in rats and mice. Arch. Biochem. Biophys. 28:132–138.

    Article  Google Scholar 

  • Huan, J. Y., Streicher, J. M., Bleyle, L. A., and Koop. D. R. 2004. Proteasome-dependent degradation of cytochromes P4502E1 and 2B1 expressed in tetracycline-regulated Hela cells. Toxicol. Appl. Pharamcol. 199:332–343.

    Article  CAS  Google Scholar 

  • Iimuro, Y., Bradford, B. U., Yamashina, S., Rusyn, I., Nakagami, M., Enomoto, N., Kono, H., Frey, W., Forman, D., Brenner, D., and Thurman, R. G. 2000. The glutathione precursor L-2-oxothiazolidine-4- carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology 31:391–398.

    Article  PubMed  CAS  Google Scholar 

  • Ingelman-Sundberg, M., Johansson, I., Penttilä, K. E., Glaumann, H., and Lindros, K. O. 1988. Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. Biochem. Biophys. Res. Commun. 157:55–60.

    Article  PubMed  CAS  Google Scholar 

  • Itoga, S., Nomura, F., Harada, S., Tsusumi, M., Takase, S., and Nakai, T. 1999. Mutation in the exon and exon–intron junction regions of human cytochrome P4502E1 gene and alcoholism. Alcoholism Clin. Exp. Res. 23:13S–16S.

    Article  CAS  Google Scholar 

  • Jarvelainen, H. A., Fang, C., Ingelman-Sundberg, M., Lukkan, T. A., Sippel, H., and Lindros, K. O. 2000. Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1 induction but not inflammatory responses in rat liver. J. Hepatol. 32:900–910.

    Article  PubMed  CAS  Google Scholar 

  • Jeong, K. S., Lee, I. J., Roberts, B. J., Soh, Y., Yoo, J. K., Lee, J. W., and Song, B. J. 1996. Transcriptional inhibition of cytochrome P4502E1 by a synthetic compound, YH 439. Arch. Biochem. Biophys. 326:137–144.

    Article  PubMed  CAS  Google Scholar 

  • Johansson, I., Ekstrom, G., Scholte, B., Puzycki, D., Jorvall, H., and Ingelman-Sundberg, M. 1988. Ethanol, fasting and acetone-inducible cytochromes P450 in rat liver. Biochemistry 27:1925–1934.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kehrer J. P. 1993. Free radicals as mediators of tissue injury and disease. Crit. Rev. Toxicol. 23:21–48.

    Article  PubMed  CAS  Google Scholar 

  • Kessova, I., Ho,Y., Thung, S., and Cederbaum, A. I. 2003. Alcohol-induced liver injury in mice lacking copper,zinc superoxide dismutase. Hepatology 38:1136–1145.

    Article  PubMed  CAS  Google Scholar 

  • Kim, N. D., Kwak, M. K., and Kim, S. G. 1997. Inhibition of cytochrome P4502E1 expression by 2-(allylthio) pyrazine a protential chemo-protective agent: hepatoprotective effects. Biochem. Pharmacol. 53:261–269.

    Article  PubMed  CAS  Google Scholar 

  • Klein, S. M., Cohen, G., Lieber, C. S., and Cederbaum, A. I. 1983. Increased microsomal oxidation of hydroxyl radical scavenging agents and ethanol after chronic consumption of ethanol. Arch. Biochem. Biophys. 223:425–433.

    Article  PubMed  CAS  Google Scholar 

  • Knecht, K. T., Thurman, R. G., and Mason, R. P. 1993. Role of superoxide and trace transition metals in the production of α-hydroxyethyl radical from ethanol by microsomes from alcohol dehydrogenase-deficient deermice. Arch. Biochem. Biophys. 303:339–348.

    Article  PubMed  CAS  Google Scholar 

  • Knecht, K. T., Adachi, Y., Bradford, B., Iimuro, Y., Kadiiska, M., Qun-Hue, X., and Thurman, R. G. 1995. Free radical adducts in the bile of rats treated chronically with intragastric alcohol. Mol. Pharmacol. 47:1028–1034.

    PubMed  CAS  Google Scholar 

  • Knight J. A. 1998. Free radicals: their history and current status in aging and disease. Ann. Clin. Lab. Sci. 28:331–346.

    PubMed  CAS  Google Scholar 

  • Kono, H., Bradford, B. U., Yin, M., Sulik, K. K., Koop, D. R., Peters, J. M., Gonzalez, F. J., McDonald, T., Dikalova, A., Kadiiska, M. B., Mason, R. P., and Thurman, R. G. 1999. CYP2E1 is not involved in early alcohol-induced liver injury. Am. J. Physiol. 277:G1259–G1267.

    PubMed  CAS  Google Scholar 

  • Koop, D. R. 1992. Oxidative and reductive metabolism by cytochrome P4502E1. FASEB J. 6:724–730.

    PubMed  CAS  Google Scholar 

  • Koop, D. R., and Casazza, J. P. 1985. Identification of ethanol-inducible P-450 isozyme 3a as the acetone and acetol monooxygenase of rabbit microsomes. J. Biol. Chem. 260:13607–13612.

    PubMed  CAS  Google Scholar 

  • Koop, D. R., and Tierney, D. J. 1990. Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. Bioessay 12:429–435.

    Article  CAS  Google Scholar 

  • Koop, D. R., Morgan, E. T., Tarr, G. E., and Coon, M. J. 1982. Purification and characterization of a unique isozyme of cytochrome P450 from liver microsomes of ethanol-treated rabbits. J. Biol. Chem. 257:8472–8480.

    PubMed  CAS  Google Scholar 

  • Koop, D. R., Chernosky, A., and Brass, E. P. 1991. Identification and induction of cytochrome P4502E1 in rat Kupffer cells. J. Pharmacol. Exp. Ther. 258:1072–1076.

    PubMed  CAS  Google Scholar 

  • Koop, D. R., Klopfenstein, B., Iimuro, Y., and Thurman, R. G. 1997. Gadolinium chloride blocks alcohol-dependent liver tocicity in rats treated chronically with intragastric alcohol despite the induction of CYP2E1. Mol. Pharmacol. 51:944–950.

    PubMed  CAS  Google Scholar 

  • Korourian, S., Hakkak, R., Ronis, M. J., Shelnut, S. R., Waldron, J., Ingelman-Sundberg, M., and Badger, T. M. 1999. The effects of enteral nutrition and chronic alcohol on hepatic necrosis. Toxicol. Sci. 47:110–117.

    Article  PubMed  CAS  Google Scholar 

  • Kukielka, E., and Cederbaum, A. I. 1994. DNA strand cleavage as a sensitive assay for the production of hydroxyl radical by microsomes: role of CYP2E1 in the increased activity after ethanol treatment. Biochem. J. 302:773–779.

    PubMed  CAS  Google Scholar 

  • Kuthan, H., and Ullrich, V. 1982. Oxidase and oxygenase function of the microsomal cytochrome P450 monooxygenase system. Eur. J. Biochem. 126:583–588.

    Article  PubMed  CAS  Google Scholar 

  • Laethem, R. M., Balazy, M., Falck, J. R., Laethem, C. L., and Koop, D. R. 1993. Formation of 19(S)-, 19(R)-, and 18(R)- hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1. J. Biol. Chem. 268:12912–12918.

    PubMed  CAS  Google Scholar 

  • Lander, H. M. 1997. An essential role for free radicals and derived species in signal transduction. FASEB J. 11:118–124.

    PubMed  CAS  Google Scholar 

  • Leclereq, I. A., Farrell G. C., Field, J., Bell, D. R., Gonzalez, F. J., and Robertson, G. R. 2000. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J. Clin. Invest.105:1067–1075.

    Article  Google Scholar 

  • Lee, S. S. T., Buters, J. T. M., Pineau, T., Fernandez-Salguero, P., and Gonzalez, F. J. 1996. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem. 271:12063–12067.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, D. F. V., and Pratt, J. M. 1998. The P450 catalytic cycle and oxygenation mechanism. Drug Metab. Rev. 30:739–786.

    Article  PubMed  CAS  Google Scholar 

  • Li, J., French, B. A., Riley, N., Bardag-Gorce, F., Fu, P., and French, S. W. 2001. Oral low carbohydrate liquid diet induces experimental steatohepatitis in the rat. Exp. Mol. Pathol. 71:132–136.

    Article  PubMed  CAS  Google Scholar 

  • Lieber, C. S. 1997. Cytochrome P4502E1; its physiological and pathological role. Physiol. Rev. 77:517–544.

    PubMed  CAS  Google Scholar 

  • Lieber, C. S. 1999. Microsomal ethanol oxidizing system: the first 30 years – a review. Alcohol. Clin. Exp. Res. 23:991–1007.

    PubMed  CAS  Google Scholar 

  • Lieber, C. S., and DeCarli, L. M. 1972. The role of the hepatic microsomal ethanol oxidizing system for ethanol metabolism in vivo. J. Pharmacol. Exp. Ther. 181:279–287.

    PubMed  CAS  Google Scholar 

  • Lieber, C. S., Leo, M. A., Aleynik, S. I., Aleynik, M. K., and DeCarli, L. M. 1997. Polyenylphosphatidylcholine decreases alcohol-induced oxidative stress in the baboon. Alcohol. Clin. Exp. Res. 21:375–379.

    Article  PubMed  CAS  Google Scholar 

  • Lindros K., and Jarvelainen, H. 1998. A new oral low-carbohydrate alcohol liquid diet producing liver lesions: a preliminary account. Alcohol 33:347–353.

    CAS  Google Scholar 

  • Loeper, J., Descatoire, V., Maurice, M., Beaune, P., Feldmann, G., Larrey, D., and Pessayre, D. 1990. Presence of functional cytochrome P-450 on isolated rat hepatocytes plasma membrane. Hepatology 11:850–858.

    Article  PubMed  CAS  Google Scholar 

  • Loeper, J., Decatoire, V., Maurice, M., Beaune, P., Belghiti, J., Houssin, D., Ballet, F., Feldmann G., Guengerich, F. P., and Pessayre, D. 1993. Cytochromes P-450 in human hepatocytes plasma membrane: recognition by several autoantibodies. Gastroeterology 104:203–216.

    CAS  Google Scholar 

  • Loida, P. J., and Sligar, S. G. 1993. Molecular recognition in cytochrome P450: mechanism for the control of uncoupling reactions. Biochemistry 32:11530–11538.

    Article  PubMed  CAS  Google Scholar 

  • Lytton, S. D., Helander, A., Zhang-Gouillon, Z. Q., Stokkeland K., Bordone R., Arico, S., Albano, E., French, S. W., and Ingelman-Sundberg, M. 1999. Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics. Mol. Pharmacol. 55:223–233.

    PubMed  CAS  Google Scholar 

  • Mari, M., and Cederbaum, A. I. 2000. CYP2E1 overexpression in HepG2 cells induces glutathione synthesis by transcriptional activation of glutamyl cysteine synthetase. J. Biol. Chem. 275:15563–15571.

    Article  PubMed  CAS  Google Scholar 

  • Mari, M., and Cederbaum, A. I. 2001. Induction of catalase, alpha and microsomal glutathione S-transferases in CYP2E1-overexpressing HepG2 cells and protection against short-term oxidative stress. Hepatology 33:652–661.

    Article  PubMed  CAS  Google Scholar 

  • Mari, M., Bai, J., and Cederbaum, A. I. 2002. Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartments protects against toxicity caused by glutathione depletion in HepG2 cells expressing CYP2E1. J. Pharmacol. Exp. Ther. 301:111–118.

    Article  PubMed  CAS  Google Scholar 

  • McCarty, M. F. 2001. Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol. Med. Hypothesis 56:8–11.

    Article  CAS  Google Scholar 

  • McCord, J. 1998. Iron, free radicals and oxidative injury. Semin. Hematol. 35:5–12.

    PubMed  CAS  Google Scholar 

  • McGehee, R. E., Jr. Ronis, M. J. J., Cowherd, R. M., Ingelman-Sundberg, M., and Badger, T. M. 1994. Characterization of cytochrome P450-2E1 induction in a rat hepatoma FGC-4 cell model by ethanol. Biochem. Pharmacol. 48:1823–1833.

    Article  PubMed  CAS  Google Scholar 

  • Morel, Y., and Barouki, R. 1999. Repression of gene expression by oxidative stress. Biochem. J. 342:481–496.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, K., French, S. W., and Morgan, T. R. 2002. Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage. Hepatology 36:122–134.

    Article  PubMed  CAS  Google Scholar 

  • Morimoto, M., Hagbjork, A. L., Nanji, A. A., Ingelman-Sundberg, M., Lindros, K. O., Fu, P. C., Albano, E., and French, S. W. 1993. Role of cytochrome P450 2E1 in alcoholic liver disease pathogenesis. Alcohol 10:459–464.

    Article  PubMed  CAS  Google Scholar 

  • Morimoto, M., Zern, M. A., Hagbjork, A. L., Ingelman-Sundberg, M., and French, S. W. 1994. Fish oil, alcohol and liver pathology: role of cytochrome P450 2E1. Proc. Soc. Exp. Biol. Med. 207:197–205.

    Google Scholar 

  • Morimoto, M., Hagbjork, A. L., Wan, Y. J., Fu, P. C., Clot, P., Albano, E., Ingelman-Sundberg, M., and French, S. W. 1995. Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. Hepatology 21:1610–1617.

    PubMed  CAS  Google Scholar 

  • Nakazawa, J., Genka, C., and Fujishima, M. 1996. Pathological aspects of active oxygens/free radicals. Jpn. J. Physiol. 46:15–32.

    Article  PubMed  CAS  Google Scholar 

  • Nanji, A. A., Zhao, S., Sadrzadeh S. M. H., Dannenberg, A. J., Tahan, S. R., and Waxman, D. J. 1994. Markedly enhanced cytochrome P4502E1 induction and lipid peroxidation is associated with severe liver injury in fish oil–ethanol-fed rats. Alcohol. Clin. Exp. Res 18:1280–1285.

    Article  PubMed  CAS  Google Scholar 

  • Nebert, D. W., Nelson, D. R., Coon, M. J., Estabrook, R. W., Feyereisen, R., Fujii-Kuriyama, Y., Gonzalez, F. J., Guengerich, F. A. P., Gunsalus, I. C., and Johnson, E. F. 1991. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 10:1–14.

    Article  PubMed  CAS  Google Scholar 

  • Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., Gunsalus, I. C., and Nebert, D. W. 1996. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1–42.

    Article  PubMed  CAS  Google Scholar 

  • Neve, E. P. A., and Ingelman-Sundberg, M. 1999. A soluble NH2-terminally truncated catalytically active form of rat cytochrome P450 2E1 targeted to liver mitochondria. FEBS Lett. 460:309–314.

    Article  PubMed  CAS  Google Scholar 

  • Neve, E. P. A., and Ingelman-Sundberg, M. 2000. Molecular basis for the transport of cytochrome P450 2E1 to the plasma membrane. J. Biol. Chem. 275: 17130–17135.

    Article  PubMed  CAS  Google Scholar 

  • Neve, E. P. A., Eliasson, E., Pronzato, M. A., Albano, E., Marinari, U., and Ingelman-Sundberg, M. 1996. Enzyme-specific transport of rat liver cytochrome P450 to the golgi apparatus. Arch. Biochem. Biophys. 333:459–465.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Nieto, N., Friedman, S. L., and Cederbaum, A. I. 2002b. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P4502E1-derived reactive oxygen species. Hepatology 35:62–73.

    Article  CAS  Google Scholar 

  • Nieto, N., Mari, M., and Cederbaum, A. I. 2003. Cytochrome P4502E1 responsiveness in the promoter of glutamate-cysteine ligase catalytic subunit. Hepatology 37:96–106.

    Article  PubMed  CAS  Google Scholar 

  • Nordman, R., Riviere, C., and Rouach, H. 1992. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Rad. Biol. Med. 12:219–240.

    Article  Google Scholar 

  • Orrenius S., Ankarcrona M., and Nicotera, P. 1996. Mechanisms of calcium-related cell death. Adv. Neurol. 71:137–151.

    PubMed  CAS  Google Scholar 

  • Peng, H. M., and Coon, M. J. 1998. Regulation of rabbit cytochrome P-450 2E1 expression in HepG2 cells by insulin and thyroid hormone. Mol. Pharmacol. 54:740–747.

    PubMed  CAS  Google Scholar 

  • Perez, M. J., and Cederbaum, A. I. 2001. Spin trapping agents (TEMPOL and POBN) protect HepG2 cells over-expressing CYP2E1 against arachidonic acid toxicity. Free Rad. Biol. Med. 30:734–746.

    Article  PubMed  CAS  Google Scholar 

  • Perez, M. J., and Cederbaum, A. L. 2003. Proteasome inhibition potentiates CYP 2E1-mediated toxicity in HepG2 cells. Hepatology 37:1395–1404.

    Article  PubMed  CAS  Google Scholar 

  • Porter, T. D., and Coon, M. J. 1991. Cytochrome P450: multiplicity of isoforms, substrates and catalytic and regulatory mechanisms. J. Biol. Chem. 266:13469–13472.

    PubMed  CAS  Google Scholar 

  • Puntarulo, S., and Cederbaum A. I. 1988. Increased NADPH-dependent chemiluminescence by microsomes after chronic ethanol consumption. Arch. Biochem. Biophys. 266:435–445.

    Article  PubMed  CAS  Google Scholar 

  • Rao, D. N. R., Yang, M. X., Lasker, J. M., and Cederbaum, A. I. 1996. 1-Hydroxyethyl radical formation during NADPH- and NADH-dependent oxidation of ethanol by human liver microsomes. Mol. Pharmacol. 49:814–821.

    PubMed  CAS  Google Scholar 

  • Rashba-Step, J., Turro, N. J., and Cederbaum, A. I. 1993. Increased NADPH- and NADH-dependent production of superoxide and hydroxyl radical by microsomes after chronic ethanol treatment. Arch. Biochem. Biophys. 300:401–408.

    Article  PubMed  CAS  Google Scholar 

  • Raucy, J. L., Lasker, J. M., Kramer, J. C., Salazer, D. E., Lieber, C. S., and Corcoran, G. B. 1991. Induction of P-450IIE1 in the obese rat. Mol. Pharmacol. 39:275–280.

    PubMed  CAS  Google Scholar 

  • Raucy, J. L., Kraner, J. C., and Lasker, J. M. 1993. Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. Crit. Rev. Toxicol. 23:1–20.

    Article  PubMed  CAS  Google Scholar 

  • Reid, A. E. 2001. Nonalcoholic steatohepatitis. Gastroenterology 121:710–723.

    Article  PubMed  CAS  Google Scholar 

  • Reinke, L., Lai, E. K., DuBose, C. M., McCay, P. B., and Janzen, E. G. 1987. Reactive free radical generation in vivo in heart and liver of ethanol fed rats: correlations with radical formation in vitro. Proc. Natl. Acad. Sci. U.S.A. 84:8223–8227.

    Google Scholar 

  • Rendic, S., and DiCarlo, F. 1997. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29:413–580.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, B. J. 1997. Evidence of proteasome-mediated cytochrome P450 degradation. J. Biol. Chem. 272:9771–9778.

    PubMed  CAS  Google Scholar 

  • Roberts, B. J., Shoaf, S. E., Jeong, K. S., and Song, B. J. 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 hours or less. Biochem., Biophys. Res. Commun. 205:1064–1071.

    Article  CAS  Google Scholar 

  • Roberts, B. J., Shoaf, S. E., and Song, B. J. 1995. Rapid changes in cytochrome P4502E1 (CYP2E1) activity and other P40 isozymes following ethanol withdrawal in rat. Biochem. Pharmacol. 49:1665–1673.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, B. J., Song, B. J., Soh, Y., Park, S. S., and Shoaf, S. E. 1995. Ethanol induces CYP2E1 by protein stabilization: role of ubiquitin conjugation in the rapid degradation for CYP2E1. J. Biol. Chem. 270:29632–29635.

    Article  PubMed  CAS  Google Scholar 

  • Robertson, G. R., Leclereq, I. A., and Farrell, G. C. 2001. Nonalcoholic steatohepatitis II: cytochrome P-450 enzymes and oxidative stress. Am. J. Physiol. Gastrointest. Liver Physiol. 281:G1135–G1139.

    PubMed  CAS  Google Scholar 

  • Ronis, M. J. J., Johansson, I., Hultenby, K., Lagercrants, J., Glaumann, H., and Ingelman-Sundberg, M. 1991. Acetone-regulated synthesis and degradation of cytochrome P4502E1 and cytochrome 2B1 in rat liver. Eur. J. Biochem. 198:383–389.

    Article  PubMed  CAS  Google Scholar 

  • Ronis, M. J. J., Huange, J., Crouch, J., Mercadao, C., Irby, D., Valentine, C. R., Lumpkin, C. K., Ingelman-Sundberg, M., and Badger, T. M. 1993. Cytochrome P450 CYP2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats. J. Pharmacol. Exp. Ther. 264:944–950.

    PubMed  CAS  Google Scholar 

  • Ronis, M. J. J., Lindros K. O., and Ingelman-Sundberg, M. 1996. The CYP2E subfamily. In Cytochromes P450. Metabolic and Toxicological Aspects, ed. C. Ioannides, pp. 211–239. New York: CRC Press.

    Google Scholar 

  • Rosen, G. M., Pou, S., Ramos, C. L., Cohen, M. S., and Britigan, B. E. 1995. Free radicals and phagocytic cells. FASEB J. 9:200–209.

    PubMed  CAS  Google Scholar 

  • Sakurai, K., and Cederbaum, A. I. 1998. Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells expressing CYP2E1. Mol. Pharmacol. 54:1024–1035.

    PubMed  CAS  Google Scholar 

  • Salmela, K. S., Kessova, I. G., Tsyrlov, I. B., and Lieber, C. S. 1998. Respective roles of human cytochrome P-4502E1, 1A2, and 3A4 in the hepatic microsomal ethanol oxidizing system. Alcohol. Clin. Exp. Res. 22:2125–2132.

    Article  PubMed  CAS  Google Scholar 

  • Shimojo, N., Ishizaki, T., Imaoka, S., Funae, Y., Fujii, S., and Okuda, K. 1993. Changes in amounts of cytochrome P-450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes. Biochem. Pharmacol. 46:621–627.

    Article  PubMed  CAS  Google Scholar 

  • Sohn, D. H., Yun, Y. P., Park, K. S., Veech, R. L., and Song, B. J. 1991. Posttranscriptional reduction of cytochrome P450IIE1 by CC14 its substrate. Biochem. Biophys. Res. Commun. 179:449–454.

    Article  PubMed  CAS  Google Scholar 

  • Song, B. J. 1995. Gene structure and multiple regulations of the ethanol-inducible cytochrome P4502E1 (CYP2E1) subfamily. In Alcohol and Hormones, vol. 6., ed. R. R. Watson, pp. 177–192. Totowa: Humana Press.

    Chapter  Google Scholar 

  • Song, B. J., Gelboin, H. V., Park, S. S., Yang, C. S., and Gonzalez, F. J. 1986. Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P450s: transcriptional and posttranscriptional regulation of the rat enzyme. J. Biol. Chem. 261:16689–16697.

    PubMed  CAS  Google Scholar 

  • Song, B. J., Matsunaga, T., Hardwich, J. P., Park, S. S., Veech, R. L., Yang, C. S., Gelboin, H. V., and Gonzalez, F. J. 1987. Stabilization of cytochrome P450 J mRNA in the diabetic rat. Mol. Endocrinol. 1:542–547.

    Article  PubMed  CAS  Google Scholar 

  • Song, B. J., Veech, R. L., Park, S. S., Gelboin, H. V., and Gonazalez, F. J. 1989. Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. J. Biol. Chem. 264:3568–3572.

    PubMed  CAS  Google Scholar 

  • Song , B. J., Cederbaum, A. I., Koop, D. R., Ingelman-Sundberg, M., and Nanji, A. 1996. Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance. Alcohol. Clin. Exp. Res. 20(Suppl.):138A–146A.

    Article  PubMed  CAS  Google Scholar 

  • Susin, S. A., Zamzami, N., and Kroemer, G. 1998. Mitochondria as regulators of apoptosis: doubt no more. Biochim. Biophys. Acta 1366:151–165.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, E., Terada, M., and Misawa, S. 2000. Cytochrome P450 2E1: its clinical and toxicological role. J. Clin. Pharm. Ther. 25:165–175.

    Article  PubMed  CAS  Google Scholar 

  • Terelius, Y., and Ingelman-Sundberg, M. 1986. Metabolism of n-pentane by ethanol-inducible cytochrome P-450 in liver microsomes and reconstituted membrane. Eur. J. Biochem. 161:303–308.

    Article  PubMed  CAS  Google Scholar 

  • Terelius, Y., Norsten-Hoog, C., Cronholm, T., and Ingelman-Sundberg, M. 1991. Acetaldehyde as a substrate for ethanol-inducible cytochrome P-450 (CYP2E1). Biochem. Biophys. Res. Commun. 179:689–694.

    Article  PubMed  CAS  Google Scholar 

  • Teschke, R., Moreno, F., and Petrides, A. S. 1981. Hepatic microsomal ethanol oxidizing system (MEOS): respective roles of ethanol and carbohydrates for the enhanced activity after chronic alcohol consumption. Biochem. Pharmacol. 30:1745–1751.

    Article  PubMed  CAS  Google Scholar 

  • Tierney, D. J., Haas, A. L., and Koop, D. R. 1992. Degradation of cytochrome P4502E1: selective loss after labilization of the enzyme. Arch. Biochem. Biophys. 293:9–16.

    Article  PubMed  CAS  Google Scholar 

  • Toykuni, S. 1999. Reactive oxygen species-induced molecular damage and its application in pathology. Pathology Inter. 49:91–102.

    Article  Google Scholar 

  • Trost, L. C., and Lemasters, J. J. 1996. The mitochondrial permeability transition: a new pathophysiological mechanism for Reye’s syndrome and toxic liver injury. J. Pharmacol. Exp. Ther. 278:1000–1005.

    PubMed  CAS  Google Scholar 

  • Tsukamoto, H. 2000. CYP2E1 and ALD. Hepatology 32:154–155.

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto, H., and Lu, S. C. 2001. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 15:1335–1349.

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto, H., Horne, W., Kamimura, S., Niemela, O., Parkkila, S., Yla- Herttuala, S., and Brittenham, G. M. 1995. Experimental liver cirrhosis induced by alcohol and iron. J. Clin. Invest. 96:620–630.

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi, M., Lasker, J., Shimizu, M., Rosman, A. S., and Lieber, C. S. 1989. The interlobular distribution of ethanol-inducible P4502E1 in rat and human liver. Hepatology 10:437–446.

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi, M, Lasker, J. M., Takahasi, T., and Lieber, C. S. 1993. In vivo induction of hepatic P4502E1 by ethanol: role of increased enzymes synthesis. Arch. Biochem. Biophys. 394:209–218.

    Article  Google Scholar 

  • Wang, M., Chanas, B., and Ghanayem, B. I. 2002. Cytochrome P4502El is essential for acrylonitrile metabolism to cyanide: comparative studies using CYP2E1-null and wild-type mice. Drug Metab. Disp. 30:911–917.

    Article  CAS  Google Scholar 

  • Weltman, M., Farrell, G., Hall P., Ingelman-Sundberg, M., and Liddle, C. 1998. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 27:128–133.

    Article  PubMed  CAS  Google Scholar 

  • Wheeler, M. D., and Thurman, R. G. 2001. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Free Rad. Biol. Med. 31:1544–1549.

    Article  PubMed  CAS  Google Scholar 

  • White, R. E. 1991. The involvement of free radicals in the mechanisms of monooxygenases. Pharmacol. Ther. 49:21–42.

    Article  PubMed  Google Scholar 

  • Winters, D. K., and Cederbaum, A. I. 1992. Time course characterization of the induction of cytochrome P450 2E1 by pyrazole and 4-methylpyrazole. Biochim. Biophys. Acta. 1117:15–24.

    Article  PubMed  CAS  Google Scholar 

  • Wolf, K. K., Wood, S. G., Bement, J. L, Sinclair, P. R., Wrighton, S. A., Jeffery, E., Gonzalez, F. J., and Sinclair, J. F. 2004. Role of mouse CYP2E1 in the o-hydroxylation of p-nitrophenol. Drug Metab. Disp. 32:681–684.

    Article  CAS  Google Scholar 

  • Woodcroft, K. J., and Novak, R. F. 1997. Insulin effects on CYP 2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes. Chem. Biol. Interact. 107:75–91.

    Article  PubMed  CAS  Google Scholar 

  • Woodcroft, K. J., Hafner, M. S., and Novak, R. F. 2002. Insulin signaling in the transcriptional and posttranscriptional regulation of CYP 2E1 expression. Hepatology 35:263–273.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 1992. Presence of functionally active cytochrome P-450IIE1 in the plasma membrane of rat hepatocytes. Hepatology 15:515–524.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 1993a. Combined effects of streptozotocin-induced diabetes plus-4 methylpyrazole treatment on rat liver cytochrome P450 2E1. Arch. Biochem. Biophys. 302:175–182.

    Article  CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 1993b. Induction of liver cytochrome P450 2E1 by pyrazole and 4-methylpyrazole in neonatal rats. J. Pharmacol. Exp. Ther. 264:1468–1473.

    CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 1996. Ethanol toxicity to a transfected HepG2 cell line expressing human cytochrome P450 2E1. J. Biol. Chem. 271:23914–23919.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 1999. Ethanol-induced apoptosis to stable HepG2 cell lines expressing human cytochrome P450 2E1. Alcohol. Clin. Exp. Res. 23:67–76.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 2001a. Removal of glutathione produces apoptosis and necrosis in HepG2 cells overexpressing CYP2E1. Alcohol. Clin. Exp. Res. 25:619–628.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Wu, D., and Cederbaum, A. I. 2002. Cyclosporin protects against arachidonic acid toxicity in rat hepatocytes: role of CYP2E1 and mitochondria. Hepatology 35:1420–1430.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., Clejan, L. A., Potter, B., and Cederbaum, A. I. 1990. Rapid decrease of cytochrome P-450IIE1 in primary hepatocyte culture and its maintenance by added 4-methypyrazole. Hepatology 12:1379–1389.

    Article  PubMed  CAS  Google Scholar 

  • Wu, Y., Salmela, K., and Lieber, C. S. 1998. Microsomal acetaldehyde oxidation is negligible in the presence of ethanol. Alcohol. Clin. Exp. Res. 22:1165–1169.

    Article  PubMed  CAS  Google Scholar 

  • Yang, M. X., and Cederbaum, A. I. 1997a. Characterization of cytochrome P450 2E1 turnover in transfected HepG2 cells expressing human CYP2E1. Arch. Biochem. Biophys. 341:25–33.

    Article  CAS  Google Scholar 

  • Yang, M. X., and Cederbaum, A. I. 1997b. Glycerol increases content and activity of human cytochrome P450 2E1 in a transduced HepG2 cell line by protein stabilization. Alcohol. Clin. Exp. Res. 21:340–347.

    Article  CAS  Google Scholar 

  • Yang, C. S., Yoo, J. S. H., Ishizaki, H., and Hong, J. 1990. Cytochrome P450IIE1. Roles in nitrosamine metabolism and mechanisms of regulation. Drug Metab. Rev. 22:147–159.

    Article  PubMed  CAS  Google Scholar 

  • Yin, M., Wheeler, M. D., Kono, H., Bradford, B. U., Galluci, R. M., Luster, M. I., and Thurman, R. G. 1999. Essential role of TNFα in alcohol-induced liver injury in mice. Gastroenterology 117:942–952.

    Article  PubMed  CAS  Google Scholar 

  • Yoo, J., Ning, S. M., Pantuck, C. B., Pantuck, E. J., and Yang, C. S. 1991. Regulation of hepatic microsomal cytochrome P-450 2E1 level by dietary lipids and carbohydrates in rats. J. Nutr. 121:959–965.

    PubMed  CAS  Google Scholar 

  • Yu, B. P. 1994. Cellular defenses against damage from reactive oxygen species. Physiol. Rev. 74:139–162.

    PubMed  CAS  Google Scholar 

  • Yun, Y., Casazza, J. P., Sohn, D. H., Veech, R. L., and Song, B. J. 1992. Pretranslational activation of cytochrome P450IIE during ketosis induced by a high fat diet. Mol. Pharmacol. 41:474–479.

    PubMed  CAS  Google Scholar 

  • Zhukov, A., and Ingelman-Sundberg, M. 1999. Relationship between cytochrome P450 catalytic cycling and stability. Biochem. J. 340:453–458.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

Studies in the author’s laboratory were supported by Grants from the National Institute on Alcohol Abuse and Alcoholism.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York 10029, USA

    Arthur I. Cederbaum

Authors
  1. Arthur I. Cederbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arthur I. Cederbaum .

Editor information

Editors and Affiliations

  1. School of Pharmacy, University of Wisconsin, Linden Drive 2015, Madison, 53706, U.S.A.

    Adnan Elfarra

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Cederbaum, A.I. (2008). CYP2E1 – Biochemical and Toxicological Aspects and Role in Alcohol-Induced Liver Injury. In: Elfarra, A. (eds) Advances in Bioactivation Research. Biotechnology: Pharmaceutical Aspects, vol IX. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77300-1_6

Download citation

Publish with us

Policies and ethics

Societies and partnerships

Search

Navigation