CYP2E1 - Biochemical and toxicological aspects and role in alcohol-induced liver injury

Mount Sinai Journal of Medicine

Volumn 73, Issue 4, 2006, Pages 657-672

  Cederbaum, Arthur I ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Alcohol; CYP2E1; HepG2 cells; Liver injury; Oxidative stress; Proteasome; Reactive oxygen species

Indexed keywords

ALCOHOL; CYTOCHROME P450 2E1; HYDROGEN PEROXIDE; IRON; REACTIVE OXYGEN METABOLITE; SUPEROXIDE;

ALCOHOL LIVER DISEASE; ALCOHOL METABOLISM; BIOCHEMISTRY; CATALYSIS; CELL STRAIN HEPG2; CONTROLLED STUDY; GENE EXPRESSION REGULATION; HUMAN; HUMAN CELL; MOLECULAR MECHANICS; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN POLYMORPHISM; REGULATORY MECHANISM; REVIEW; TISSUE DISTRIBUTION;

ANIMALS; CYTOCHROME P-450 CYP2E1; CYTOCHROME P-450 ENZYME SYSTEM; ETHANOL; GENE EXPRESSION REGULATION; HUMANS; LIVER; LIVER DISEASES, ALCOHOLIC; MICROSOMES, LIVER; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 33746329952     PISSN: 00272507     EISSN: 00272507     Source Type: Journal    
DOI: None     Document Type: Review

References (144)

1. Guengerich FP. Mammalian cytochrome P450, Boca Raton, FL: CRC Press; 1987.
2. Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6(1):1-42.
3. Porter TD, Coon MJ. Cytochrome P450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 1991; 266(21):13469-13472.
4. Guengerich FP. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 2001; 14(6):611-650.
5. Lewis DF, Pratt JM. The P450 catalytic cycle and oxygenation mechanism. Drug Metab Rev 1998; 30(4):739-786.
6. Loida PJ, Sligar SG. Molecular recognition in cytochrome P450: mechanism for the control of uncoupling reactions. Biochemistry 1993; 32(43):11530-11538.
7. White RE. The involvement of free radicals in the mechanisms of monooxygenases. Pharmacol Ther 1991; 49(1-2):21-42.
8. Knight JA. Free radicals: their history and current status in aging and disease. Ann Clin Lab Sci 1998; 28(6):331-346.
9. Kehrer JP. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 1993; 23(1):21-48.
10. Nordmann R, Ribiere C, Rouach H. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 1992; 12(3):219-240.
11. Halliwell B. Antioxidant defense mechanisms: from the beginning to the end (of the beginning). Free Radic Res 1999; 31(4):261-272.
12. Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74(1):139-162.
13. Rosen GM, Pou S, Ramos CL, et al. Free radicals and phagocytic cells. FASEB J 1995; 9(2):200-209.
14. Lander HM. An essential role for free radicals and derived species in signal transduction. FASEB J 1997; 11(2):118-124.
15. Cederbaum AI. Introduction-serial review: alcohol, oxidative stress and cell injury. Free Radic Biol Med 2001; 31(12):1524-1526.
16. Bondy SC. Ethanol toxicity and oxidative stress. Toxicol Lett 1992; 63; 231-242.
17. Iimuro Y, Bradford Bu, Yamashina S, et al. The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology 2000; 31(2):391-398.
18. Nanji AA, Zhao S, Sadrzadeh SM, et al. 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 1994; 18(5):1280-1285.
19. Morimoto M, Zern MA, Hagbjork Al. et al. Fish oil, alcohol, and liver pathology: role of cytochrome P450 2E1. Proc Soc Exp Biol Med 1994; 207(2):197-205.
20. Tsukamoto H, Horne W, Kamimura S, et al. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest 1995; 96(1):620-630.
21. Knecht KT, Adachi Y, Bradford B, et al. Free radical adducts in the bile of rats treated chronically with intragastric alcohol. Mol Pharmacol 1995; 47:1028-1034.
22. Wheeler MD, Kono H, Yin M, et al. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Free Radic Biol Med 2001; 31(12):1544-1549.
23. Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 2003; 124:778-790.
24. Tsukamoto H, Lu SC. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J 2001; 15:1335-1349.
25. Adachi M, Ishii H. Role of mitochondria in alcoholic liver injury. Free Radic Biol Med 2002; 32:487-491.
26. Bailey SM, Cunningham CC. Contribution of mitochondria to oxidative stress associated with alcoholic liver disease. Free Radic Biol Med 2002; 32:11-16.
27. Wu D, Cederbaum AI. Ethanol-induced apoptosis to stable HepG2 cell lines expressing human cytochrome P4502E1. Alcoholism Clin Exp Res 1999; 23(1):67-76.
28. Lieber CS. Microsomal ethanol oxidizing system (MEOS): the first 30 years (1968-1998) - a review. Alcohol Clin Exp Res 1999; 23(6):991-1007.
29. Lieber CS, Decarli LM. The role of the hepatic microsomal ethanol oxidizing system (MEOS) for ethanol metabolism in vivo. J Pharmacol Exp Ther 1972; 181(2):279-287.
30. Koop DR, Morgan ET, Tarr GE, Coon MJ. Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits. J Biol Chem 1982; 257(14):8472-8480.
31. Ingelman-Sundberg M, Johansson I. Penttila KE, et al. Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver. Biochem Biophys Res Commun 1988; 157(1):55-60.
32. Loeper J, Descatoire V, Maurice M, et al. Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. Hepatology 1990; 11(5);850-858.
33. Lytton SD, Helander A, Zhang-Gouillon ZQ, et al. Autoantibodies against cytochrome P-4502E1 and P-4503A in alcoholics. Mol Pharmacol 1999; 55(2):223-233.
34. Neve EP, Ingelman-Sundberg M. Molecular basis for the transport of cytochrome P450 2E1 to the plasma membrane. J Biol Chem 2000; 275(22):17130-17135.
35. 2-terminally truncated catalytically active form of rat cytochrome P450 2E1 targeted to liver mitochondria. FEBS Lett 1999; 460(2):309-314.
36. Robin MA, Anandatheerthavarada HK, Fang JK, et al. Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N terminus and requires mitochondrial specific electron transfer proteins for activity. J Biol Chem 2001; 276(27):24680-24689.
37. Koop DR, Casazza JP. Identification of ethanol-inducible P-450 isozyme 3a as the acetone and acetol monooxygenase of rabbit microsomes. J Biol Chem 1985; 260(25):13607-13612.
38. Bondoc FY, Bao Z, Hu WY, et al. Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice. Biochem Pharmacol 1999; 58(3):461-463.
39. Laethem. RM, Balazy M, Falck JR, et al. Formation of 19(S)-, 19(R)-, and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1 J Biol Chem 1993; 268(17):12912-12918.
40. Koop DR. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 1992; 6(2):724-730.
41. Raucy JL, Kraner JC, Lasker JM. Bioactivation of halogenated hydrocarbons by cytochrome P4502E1 Crit Rev Toxicol 1993; 23(1):1-20.
42. Tanaka E, Terada M, Misawa S. Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther 2000; 25(3):165-175.
43. Bolt HM, Roos PH, Thier R. The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. Int Arch Occup Environ Health 2003; 76(3):174-185.
44. Yang CS, Yoo JS, Ishizaki H, Hong JY. Cytochrome P450IIE1: roles in nitrosamine metabolism and mechanisms of regulation. Drug Metab Rev 1990; 22(2-3):147-159.
45. Girre C, Lucas D, Hispard E, et al. Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem Pharmacol 1994; 47(9):1503-1508.
46. Gorsky LD, Koop DR, Coon MJ. On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 1984; 259(11):6812-6817.
47. Ekstrom G, Ingelman-Sundberg M. Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem Pharmacol 1989; 38(8):1313-1319.
48. Rashba-Step J, Turro NJ, Cederbaum AI. Increased NADPH-and NADH-dependent production of superoxide and hydroxyl radical by microsomes after chronic ethanol treatment. Arch Biochem Biophys 1993; 300(1):401-408.
49. Kukielka E, Cederbaum AI. 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 1994; 302(3):773-779.
50. Wu YS, Salmela KS, Lieber CS. Microsomal acetaldehyde oxidation is negligible in the presence of ethanol. Alcohol Clin Exp Res 1998; 22(5):1165-1169.
51. Albano E, Tomasi A, Persson JO, et al. Role of ethanol-inducible cytochrome P450 (P450IIE1) in catalysing the free radical activation of aliphatic alcohols. Biochem Pharmacol 1991; 41(12):1895-1902.
52. Knecht KT, Thurman RG, Mason RP. Role of superoxide and trace transition metals in the production of alpha-hydroxyethyl radical from ethanol by microsomes from alcohol dehydrogenase-deficient deermice. Arch Biochem Biophys 1993; 303(2):339-348.
53. Rao DN, Yang MX, Lasker JM, Cederbaum AI. 1-Hydroxyethyl radical formation during NADPH- and NADH-dependent oxidation of ethanol by human liver microsomes. Mol Pharmacol 1996; 49(5):814-821.
54. Reinke LA, Lai EK, Dubose CM, McCay PB. Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro. Proc Natl Acad Sci U S A 1987; 84(24):9223-9227.
55. Clot P, Albano E, Eliasson E, et al. Cytochrome P4502E1 hydroxyethyl radical adducts as the major antigen in autoantibody formation among alcoholics. Gastroenterology 1996; 111(1):206-216.
56. Harada S, Agarwal DP, Nomura F, Higuchi S. Metabolic and ethnic determinants of alcohol drinking habits and vulnerability to alcohol-related disorder. Alcohol Clin Exp Res 2001; 25(5):71S-75S.
57. Itoga S, Nomura F, Harada S, et al. Mutations in the exons and exon-intron junction regions of human cytochrome P4502E1 gene and alcoholism. Alcohol Clin Exp Res 1999; 23(4):13S-16S.
58. Badger TM, Ronis MJ, Seitz HK, et al. Alcohol metabolism: role in toxicity and carcinogenesis. Alcohol Clin Exp Res 2003; 27(2):336-347.
59. Song BJ, Gelboin HV, Park SS, et al. 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 1986; 261(35):16689-16697.
60. Song BJ, Cederbaum AI, Koop DR, et al. Ethanol-inducible cytochrome P450 (CYP2E1): Biochemistry, molecular biology and clinical relevance. Alcohol Clin Exp Res 1996; 20(Suppl):138A-146A.
61. Raucy JL, Lasker JM, Kraner JC, et al. Induction of cytochrome P450IIE1 in the obese overfed rat. Mol Pharmacol 1991; 39(3):275-280.
62. Hong JY, Pan JM, Gonzalez FJ, et al. The induction of a specific form of cytochrome P-450 (P-450j) by fasting. Biochem Biophys Res Commun 1987; 142(3):1077-1083.
63. Woodcroft KJ, Hafner MS, Novak RF. Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 2002; 35(2):263-273.
64. De Waziers I, Garlatti M, Bouguet J, et al. Insulin down-regulates cytochrome P450 2B and 2E expression at the posttranscriptional level in the rat hepatoma cell line. Mol Pharmacol 1995; 47(3):474-479.
65. Woodcroft KJ, Novak RF. Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes. Chem Biol Interact 1997; 107(1-2):75-91.
66. Bellward GD, Chang T, Rodrigues B, et al. Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat. Mol Pharmacol 1988; 33(2):140-143.
67. Yoo JS, Ning SM, Pantuck CB, et al. Regulation of hepatic microsomal cytochrome P450IIE1 level by dietary lipids and carbohydrates in rats. J Nutr 1991; 121(7):959-965.
68. Lindros KO, Jarvelainen HA. A new oral low-carbohydrate alcohol liquid diet producing liver lesions: a preliminary account. Alcohol Alcohol 1998; 33(4):347-353.
69. Hong JY, Ning SM, Ma BL, et al. Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice. Arch Biochem Biophys 1990; 281(1):132-138.
70. Eliasson E, Mkrtchian S, Ingelman-Sundberg M. Hormone-and substrate-regulated intracellular degradation of cytochrome P450 (2E1) involving MgATP-activated rapid proteolysis in the endoplasmic reticulum membranes. J Biol Chem 1992; 267(22):15765-15769.
71. Hoivik DJ, Manautou JE, Tveit A, et al. Gender-related differences in susceptibility to acetaminophen-induced protein arylation and nephrotoxicity in the CD-1 mouse. Toxicol Appl Pharmacol 1995; 130(2):257-271.
72. Weltman MD, Farrell GC, Hall P, et al. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 1998; 27(1):128-133.
73. Leclercq IA, Farrell GC, Field J, et al. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 2000; 105(8):1067-1075.
74. Robertson G, Leclercq I, Farrell GC. Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol 2001; 281(5):G1135-G1139.
75. Koop DR, Tierney DJ. Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. Bioessays 1990; 12(9):429-435.
76. Song BJ, Matsunaga T, Hardwick JP, et al. Stabilization of cytochrome P450j messenger ribonucleic acid in the diabetic rat. Mol Endocrinol 1987; 1(8):542-547.
77. Song BJ, Veech RL, Park SS, et al. Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. J Biol Chem 1989; 264(6):3568-3572.
78. Eliasson E, Johansson I, Ingelman-Sundberg M. Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures. Biochem Biophys Res Commun 1988; 150(1):436-443.
79. Wu DF, Clejan L, Potter B, Cederbaum AI. Rapid decrease of cytochrome P-450IIE1 in primary hepatocyte culture and its maintenance by added 4-methylpyrazole. Hepatology 1990; 12(6):1379-1389.
80. Ronis MJ, Huang J, Crouch J, et al. Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats. J Pharmacol Exp Ther 1993; 264(2):944-950.
81. McGehee RE Jr, Ronis MJ, Cowherd RM, et al. Characterization of cytochrome P450 2E1 induction in a rat hepatoma FGC-4 cell model by ethanol. Biochem Pharmacol 1994; 48(9):1823-1833.
82. Roberts BJ, Shoaf SE, Jeong KK, Song BJ. 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 1994; 205(2):1064-1071.
83. Roberts BJ, Song BJ, Soh Y, et al. Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. J Biol Chem 1995; 270(50):29632-29635.
84. Winters DK, Cederbaum AI. Time course characterization of the induction of cytochrome P-450 2E1 by pyrazole and 4-methylpyrazole. Biochim Biophys Acta 1992; 1117(1):15-24.
85. Wu D, Cederbaum AI. Induction of liver cytochrome P4502E1 by pyrazole and 4-methylpyrazole in neonatal rats. J Pharmacol Exp Ther 1993; 264(3):1468-1473.
86. Yang MX, Cederbaum AI. Characterization of cytochrome P4502E1 turnover in transfected HepG2 cells expressing human CYP2E1. Arch Biochem Biophys 1997; 341(1):25-33.
87. Bardag-Gorce F, Li J, French BA, French SW. Ethanol withdrawal induced CYP2E1 degradation in vivo, blocked by the proteasomal inhibitor PS-341. Free Radic Biol Med 2002; 32(1):17-21.
88. Donohue TM, Zetterman RK, Zhang-Gouilon ZQ, French SW. Peptidase activities of the multicatalytic protease in rat liver after voluntary and intragastric ethanol administration Hepatology 1998; 28:486-491.
89. Fataccioli V, Andraud E, Gentil M, et al. Effects of chronic ethanol administration on rat liver proteasome activities: relationship with oxidative stress. Hepatology 1999; 29:14-20.
90. Bardag-Gorce F, Yuan QX, Li, J, et al. The effect of ethanol-induced cytochrome P450 2E1 on the inhibition of proteasome activity by alcohol. Biochem Biophys Res Commun 2000; 279:23-29.
91. Perez MJ, Cederbaum AI. Proteasome inhibition potentiates CYP 2E1-mediated toxicity in HepG2 cells. Hepatology 2003; 37:1395-1404.
92. Roberts BJ. Evidence of proteasome-mediated cytochrome P450 degradation. J Biol Chem 1997; 272(15):9771-9778.
93. Lee SS, Buters JT, Pineau T, et al. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 1996; 271(20):12063-12067.
94. Wang H, Chanas B, Ghanayem BI. Cytochrome P450 2E1 (CYP2E1) is essential for acrylonitrile metabolism to cyanide: comparative studies using CYP2E1-null and wild-type mice. Drug Metab Dispos 2002; 30(8):911-917.
95. Carlson GP. Comparison of the susceptibility of wild-type and CYP2E1 knockout mice to the hepatotoxic and pneumotoxic effects of styrene and styrene oxide. Toxicol Lett 2004; 150(3):335-339.
96. Wolf KK, Wood SG, Bement JL, et al. Role of mouse CYP2E1 in the O-hydroxylation of p-nitrophenol: comparison of activities in hepatic microsomes from Cyp2e1(-/-) and wild-type mice. Drug Metab Dispos 2004; 32(7):681-684.
97. Kono H, Bradford BU, Yin M, et al. CYP2E1 is not involved in early alcohol-induced liver injury. Am J Physiol 1999; 277(6):G1259-G1267.
98. Cheung C, Yu AM, Ward JM, et al. The cyp2e1-humanized transgenic mouse: role of CYP2E1 in acetaminophen hepatotoxicity. Drug Metab Dispos 2005; 33(3):449-457.
99. Morimoto M, Hagbjork AL, Wan YJ, et al. Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. Hepatology 1995; 21(6):1610-1617.
100. Castillo T, Koop DR, Kamimura S, et al. Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Hepatology 1992; 16(4):992-996.
101. French SW, Morimoto M, Reitz RC, et al. Lipid peroxidation, CYP2E1 and arachidonic acid metabolism in alcoholic liver disease in rats. J Nutr 1997; 127(5):907S-911S.
102. Gouillon Z, Lucas D, Li J, et al. Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole. Proc Soc Exp Biol Med 2000; 224(4):302-308.
103. Lieber CS, Leo MA, Aleynik SI, et al. Polyenylphosphatidylcholine decreases alcohol-induced oxidative stress in the baboon. Alcohol Clin Exp Res 1997; 21(2):375-379.
104. Morgan K, French SW, Morgan TR. Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage. Hepatology 2002; 36(1):122-134.
105. Yin M, Wheeler MD, Kono H, et al. Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology 1999; 117(4):942-952.
106. Koop DR, Klopfenstein B, Iimuro Y, Thurman RG. Gadolinium chloride blocks alcohol-dependent liver toxicity in rats treated chronically with intragastric alcohol despite the induction of CYP2E1. Mol Pharmacol 1997; 51(6):944-950.
107. Badger DA, Kuester RK, Sauer JM, Sipes IG. Gadolinium chloride reduces cytochrome P450: relevance to chemical-induced hepatotoxicity. Toxicology 1997; 121(2):143-153.
108. Jarvelainen HA, Fang C, Ingelman-Sundberg M, et al. Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1 induction but not inflammatory responses in rat liver. J Hepatol 2000; 32(6):900-910.
109. Tsukamoto H. CYP2E1 and ALD. Hepatology 2000; 32(1):154-156.
110. Bradford BU, Kono H, Isayama F, et al. Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver. Hepatology 2005; 41(2):336-344.
111. Dai Y, Rashba-Step J, Cederbaum AI. Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates. Biochemistry 1993; 32(27):6928-6937.
112. Chen Q, Cederbaum AI. Cytotoxicity and apoptosis produced by cytochrome P450 2E1 in HepG2 cells. Mol Pharmacol 1998; 53(4):638-648.
113. Dai Y, Cederbaum AI. Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J Pharmacol Exp Ther 1995; 273(3):1497-1505.
114. Dai Y, Cederbaum AI. Inactivation and degradation of human cytochrome P4502E1 by CC14 in a transfected HepG2 cell line. J Pharmacol Exp Ther 1995; 275(3):1614-1622.
115. Chen Q, Galleano M, Cederbaum AI. Cytotoxicity and apoptosis produced by arachidonic acid in HepG2 cells overexpressing human cytochrome P4502E1 J Biol Chem 1997; 272(23):14532-14541.
116. Sakurai K, Cederbaum AI. Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells that express cytochrome P450 2E1 Mol Pharmacol 1998; 54(6):1024-1035.
117. Wu D, Cederbaum AI. Ethanol cytotoxicity to a transfected HepG2 cell line expressing human cytochrome P4502E1. J Biol Chem 1996; 271(39):23914-23919.
118. Wu D, Cederbaum AI. Removal of glutathione produces apoptosis and necrosis in HepG2 cells overexpressing CYP2E1. Alcohol Clin Exp Res 2001; 25(4):619-628.
119. Caro AA, Cederbaum AI. Synergistic toxicity of iron and arachidonic acid in HepG2 cells overexpressing CYP2E1. Mol Pharmacol 2001; 60(4):742-752.
120. Wu D, Cederbaum AI. Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1. Mol Cell Biochem 2000; 204(1-2):157-167.
121. Wu D, Cederbaum AI. Sodium salicylate increases CYP2E1 levels and enhances arachidonic acid toxicity in HepG2 cells and cultured rat hepatocytes. Mol Pharmacol 2001; 59(4):795-805.
122. Mari M, Cederbaum AI. CYP2E1 overexpression in HepG2 cells induces glutathione synthesis by transcriptional activation of gamma-glutamylcysteine synthetase. J Biol Chem 2000; 275(20):15563-15571.
123. Nieto N, Mari M, Cederbaum AI. Cytochrome P450 2E1 responsiveness in the promoter of glutamate-cysteine ligase catalytic subunit. Hepatology 2003; 37(1):96-106.
124. Mari M, Cederbaum AI. Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress. Hepatology 2001; 33(3):652-661.
125. Nieto N, Friedman SL Cederbaum AI. Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem 2002; 277:9853-9864.
126. Nieto N, Friedman SL, Cederbaum AI. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P4502E1-derived reactive oxygen species. Hepatology 2002; 35:62-73.
127. Susin SA, Zamzami N, Kroemer G. Mitochondria as regulators of apoptosis: doubt no more. Biochim Biophys Acta 1998; 1366(1-2):151-165.
128. Orrenius S, Ankarcrona. M, Nicotera P. Mechanisms of calcium-related cell death. Adv Neurol 1996; 71:137-151.
129. Trost LC, Lemasters JJ. The mitochondrial permeability transition: a new pathophysiological mechanism for Reye's syndrome and toxic liver injury. J Pharmacol Exp Ther 1996; 278(3):1000-1005.
130. Mari M, Bai J, Cederbaum AI. Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against toxicity caused by glutathione depletion in HepG2 cells expressing CYP2E1. J Pharmacol Exp Ther 2002; 301(1):111-118.
131. Perez MJ, Cederbaum AI. Spin trapping agents (Tempol and POBN) protect HepG2 cells overexpressing CYP2E1 against arachidonic acid toxicity. Free Radic Biol Med 2001; 30(7):734-746.
132. Bai J, Cederbaum AI. Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells. J Biol Chem 2001; 276(6):4315-4321.
133. Wu D, Cederbaum AI. Cyclosporine A protects against arachidonic acid toxicity in rat hepatocytes: role of CYP2E1 and mitochondria. Hepatology 2002; 35(6):1420-1430.
134. Gong P, Hu B, Cederbaum AI. Diallyl sulfide induces heme oxygenase-1 through MAPK pathway. Arch Biochem Biophys 2004; 432(2):252-260.
135. Caro AA, Cederbaum AI. Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol 2005; 69(7):1081-1093.
136. Choi EY, Kim SG, Lee JW, et al. Suppression of rat hepatic cytochrome P450 2E1 expression by isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl] acetate (YH439), an experimental hepatoprotectant: protective role against hepatic injury. Biochem Pharmacol 1996; 52(8):1219-1225.
137. Jeong KS, Lee U, Roberts BJ, et al. Transcriptional inhibition of cytochrome P4502E1 by a synthetic compound, YH439. Arch Biochem. Biophys 1996; 326(1):137-144.
138. Barcelo S, Gardiner JM, Gescher A, Chipman JK. CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane. Carcinogenesis 1996; 17(2):277-282.
139. He K, Iyer KR, Hayes RN, et al. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 1998; 11(4):252-259.
140. McCarty MF. Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol. Med Hypotheses 2001; 56(1):8-11.
141. Donohue TM Jr, Zetterman RK, Zhang-Gouillon ZQ, French SW. Peptidase activities of the multicatalytic protease in rat liver after voluntary and intragastric ethanol administration. Hepatology 1998; 28(2):486-491.
142. Huan JY, Streicher JM, Bleyle LA, Koop DR. Proteasome-dependent degradation of cytochromes P450 2E1 and 2B1 expressed in tetracycline-regulated HeLa cells. Toxicol Appl Pharmacol 2004; 199(3):332-343.
143. Goasduff T, Cederbaum AI. CYP2E1 degradation by in vitro reconstituted systems: role of the molecular chaperone hsp90. Arch Biochem Biophys 2000; 379(2):321-330.
144. Wen F, Abdalla MY, Aloman C, et al. Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1. J Mes Virol 2004; 72(2):230-240.