Mechanisms and cell signaling in alcoholic liver disease

Biological Chemistry

Volumn 391, Issue 11, 2010, Pages 1249-1264

  Beier, Juliane I ^a,b   McClain, Craig J ^a,b,c  

^a University of Louisville School of Medicine   (United States)

^b UNIVERSITY OF LOUISVILLE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

alcohol metabolism; alcoholic liver disease; cytokines; inflammation; oxidative stress

Indexed keywords

ACETALDEHYDE; ACETYL COENZYME A; ADENOSINE PHOSPHATE; ALCOHOL DEHYDROGENASE; ALDEHYDE DEHYDROGENASE; CASPASE 3; CASPASE 8; CD14 ANTIGEN; COPPER ZINC SUPEROXIDE DISMUTASE; CYCLIC AMP; CYTOCHROME P450 2E1; CYTOKINE; FAS LIGAND; LIPID PEROXIDE; LIPOPOLYSACCHARIDE; MANGANESE SUPEROXIDE DISMUTASE; MYELOID DIFFERENTIATION FACTOR 88; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PROTEIN BAX; PROTEIN BCL 2; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; S ADENOSYLMETHIONINE; STRESS ACTIVATED PROTEIN KINASE; SUPEROXIDE; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

ALCOHOL ABUSE; ALCOHOL BLOOD LEVEL; ALCOHOL LIVER CIRRHOSIS; ALCOHOL METABOLISM; ALCOHOLISM; AMINO ACID METABOLISM; FATTY ACID SYNTHESIS; FATTY LIVER; FIBRIN METABOLISM; GENE EXPRESSION; HUMAN; INFLAMMATORY CELL; KUPFFER CELL; LIPID PEROXIDATION; LIVER CELL; LIVER INJURY; LIVER TOXICITY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; STEATOSIS; STELLATE CELL; ZINC METABOLISM;

ALCOHOL DEHYDROGENASE; ALCOHOL OXIDOREDUCTASES; ALCOHOLISM; ANIMALS; CATALASE; CHRONIC DISEASE; CYTOCHROME P-450 CYP2E1; CYTOCHROME P-450 ENZYME SYSTEM; ETHANOL; FATTY LIVER, ALCOHOLIC; FREE RADICAL SCAVENGERS; GENE EXPRESSION REGULATION; HEPATITIS, ALCOHOLIC; HUMANS; LIVER CIRRHOSIS, ALCOHOLIC; MICE; MOLECULAR TARGETED THERAPY; NF-KAPPA B; NITRIC OXIDE; RATS; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN SPECIES; RISK FACTORS; S-ADENOSYLMETHIONINE; SIGNAL TRANSDUCTION; SUPEROXIDES;

EID: 78649339034     PISSN: 14316730     EISSN: 14374315     Source Type: Journal    
DOI: 10.1515/BC.2010.137     Document Type: Review

References (161)

1. Adachi, Y., Bradford, B.U., Gao, W., Bojes, H.K., and Thurman, R.G. (1994). Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology 20, 453-460.
2. Allen, R.G. and Tresini, M. (2000). Oxidative stress and gene regulation. Free Radic. Biol. Med. 28, 463-499.
3. Arteel, G.E. (2003). Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 124, 778-790.
4. Arteel, G.E. (2008). New role of plasminogen activator inhibitor-1 in alcohol-induced liver injury. J. Gastroenterol. Hepatol. 23 (Suppl. 1), S54-S59.
5. Arteel, G.E., Raleigh, J.A., Bradford, B.U., and Thurman, R.G. (1996). Acute alcohol produces hypoxia directly in rat liver tissue in vivo: role of Kupffer cells. Am. J. Physiol. 271, G494-G500.
6. Arteel, G.E., Iimuro, Y., Yin, M., Raleigh, J.A., and Thurman, R.G. (1997). Chronic enteral ethanol treatment causes hypoxia in rat liver tissue in vivo. Hepatology 25, 920-926.
7. Avila, M.A., Berasain, C., Torres, L., Martin-Duce, A., Corrales, F.J., Yang, H., Prieto, J., Lu, S.C., Caballeria, J., Rodes, J., et al. (2000). Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J. Hepatol. 33, 907-914.
8. Avila, M.A., Berasain, C., Prieto, J., Mato, J.M., Garcia-Trevijano, E.R., and Corrales, F.J. (2005). Influence of impaired liver methio-nine metabolism on the development of vascular disease and inflammation. Curr. Med. Chem. Cardiovasc. Hematol. Agents 3, 267-281.
9. Barak, A.J., Beckenhauer, H.C., Kharbanda, K.K., and Tuma, D.J. (2001). Chronic ethanol consumption increases homocysteine accumulation in hepatocytes. Alcohol 25, 77-81.
10. Bardag-Gorce, F., Yuan, Q.X., Li, J., French, B.A., Fang, C., Ingel-man-Sundberg, M., and French, S.W. (2000). The effect of eth-anol-induced cytochrome p4502E1 on the inhibition of pro-teasome activity by alcohol. Biochem. Biophys. Res. Commun. 279, 23-29.
11. Beckman, J.S. (1996). The physiological and pathophysiological chemistry of nitric oxide. In: Nitric Oxide: Principles and Actions, J. Lancaster, ed. (San Diego, CA, USA: Academic Press), pp. 1-82.
12. Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A., and Freeman, B.A. (1990). Apparent hydroxyl radical production by peroxy-nitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 87, 1620-1624.
13. Beier, J.I., Guo, L., von Montfort, C., Kaiser, J.P., Joshi-Barve, S., and Arteel, G.E. (2008). New role of resistin in lipopolysaccha-ride-induced liver damage in mice. J. Pharmacol. Exp. Ther. 325, 801-808.
14. Beier, J.I., Luyendyk, J.P., Guo, L., von Montfort, C., Staunton, D.E., and Arteel, G.E. (2009). Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide-induced liver injury caused by ethanol in mice. Hepatology 49, 1545-1553.
15. Bergheim, I., McClain, C.J., and Arteel, G.E. (2005). Treatment of alcoholic liver disease. Dig. Dis. 23, 275-284.
16. Bergheim, I., Guo, L., Davis, M.A., Duveau, I., and Arteel, G.E. (2006a). Critical role of plasminogen activator inhibitor-1 in cho-lestatic liver injury and fibrosis. J. Pharmacol. Exp. Ther. 316, 592-600. (Pubitemid 43130985)
17. Bergheim, I., Guo, L., Davis, M.A., Lambert, J.C., Beier, J.I., Duveau, I., Luyendyk, J.P., Roth, R.A., and Arteel, G.E. (2006b) Metformin prevents alcohol-induced liver injury in the mouse: critical role of plasminogen activator inhibitor-1. Gastroenterol-ogy 130, 2099-2112. (Pubitemid 43816952)
18. Best, C.H., Hartroft, W.S., Lucas, C.C., and Ridout, J.H. (1949). Liver damage produced by feeding alcohol or sugar and its prevention by choline. Br. Med. J. 2, 1001-1006.
19. Bigatello, L.M., Broitman, S.A., Fattori, L., Di Paoli, M., Pontello, M., Bevilacqua, G., and Nespoli, A. (1987). Endotoxemia, ence-phalopathy, and mortality in cirrhotic patients. Am. J. Gastroen-terol. 82, 11-15.
20. Boer, R., Ulrich, W.R., Klein, T., Mirau, B., Haas, S., and Baur, I. (2000). The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes. Mol. Pharmacol. 58, 1026-1034.
21. Boetticher, N.C., Peine, C.J., Kwo, P., Abrams, G.A., Patel, T., Aqel, B., Boardman, L., Gores, G.J., Harmsen, W.S., McClain, C.J., et al. (2008). A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology 135, 1953-1960.
22. Canto, C., and Auwerx, J. (2009). PGC-1a, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol. 20, 98-105.
23. Cao, Q., Mak, K.M., and Lieber, C.S. (2005). Cytochrome P4502E1 primes macrophages to increase TNF-a production in response to lipopolysaccharide. Am. J. Physiol. Gastrointest. Liver Phy-siol. 289, G95-G107.
24. Cederbaum, A.I., Wu, D., Mari, M., and Bai, J. (2001). CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic. Biol. Med. 31, 1539-1543.
25. Colell, A., Garcia-Ruiz, C., Miranda, M., Ardite, E., Mari, M., Morales, A., Corrales, F., Kaplowitz, N., and Fernandez-Checa, J.C. (1998). Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 115, 1541-1551.
26. Coughlin, S.R. (2000). Thrombin signalling and protease-activated receptors. Nature 407, 258-264.
27. 12 status. Nutrition 16, 296-302.
28. Cravo, M.L., Gloria, L.M., Selhub, J., Nadeau, M.R., Camilo, M.E., Resende, M.P., Cardoso, J.N., Leitao, C.N., and Mira, F.C. (1996). Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am. J. Clin. Nutr. 63, 220-224.
29. Cunningham, C.C. and Bailey, S.M. (2001). Ethanol consumption and liver mitochondria function. Biol. Signals Recept. 10, 271-282.
30. D'Angio, C.T. and Finkelstein, J.N. (2000). Oxygen regulation of gene expression: a study in opposites. Mol. Genet. Metab. 71, 371-380.
31. Day, C.P. (2000). Who gets alcoholic liver disease: nature or nurture? J. R. Coll. Physicians Lond. 34, 557-562.
32. Day, C.P. and James, O.F. (1998). Hepatic steatosis: innocent bystander or guilty party? Hepatology 27, 1463-1466.
33. De, B.K., Gangopadhyay, S., Dutta, D., Baksi, S.D., Pani, A., and Ghosh, P. (2009). Pentoxifylline versus prednisolone for severe alcoholic hepatitis: a randomized controlled trial. World J. Gas-troenterol. 15, 1613-1619.
34. De Groot, H., Noll, T., and Sies, H. (1985). Oxygen dependence and subcellular partitioning of hepatic menadione-mediated oxygen uptake. Arch. Biochem. Biophys. 243, 556-562.
35. Deaciuc, I.V., Fortunato, F., D'Souza, N.B., Hill, D.B., Schmidt, J., Lee, E.Y., and McClain, C.J. (1999). Modulation of caspase-3 activity and Fas ligand mRNA expression in rat liver cells in vivo by alcohol and lipopolysaccharide. Alcohol Clin. Exp. Res. 23, 349-356.
36. Diehl, A.M. (2002). Liver disease in alcohol abusers: clinical perspective. Alcohol 27, 7-11.
37. Donohue, T.M. Jr. (2002). The ubiquitin-proteasome system and its role in ethanol-induced disorders. Addict. Biol. 7, 15-28.
38. Droge, W. (2002). Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47-95.
39. Duplantier, J.G., Dubuisson, L., Senant, N., Freyburger, G., Lauren-deau, I., Herbert, J.M., Desmouliere, A., and Rosenbaum, J. (2004). A role for thrombin in liver fibrosis. Gut 53, 1682-1687.
40. Eastin, C.E., McClain, C.J., Lee, K., Bagby, G.J., and Chawla, R.K. (1997). Choline deficiency augments and antibody to tumor necrosis factor-a attenuates endotoxin-induced hepatic injury. Alcohol. Clin. Exp. Res. 21, 1037-1041.
41. Ekstrom, G. and Ingelman-Sundberg, M. (1989). Rat liver micro-somal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem. Pharmacol. 38, 1313-1319.
42. Ermak, G. and Davies, K.J. (2002). Calcium and oxidative stress: from cell signaling to cell death. Mol. Immunol. 38, 713-721.
43. Fausto, N. (2006). Involvement of the innate immune system in liver regeneration and injury. J. Hepatol. 45, 347-349.
44. Fearns, C. and Loskutoff, D.J. (1997). Induction of plasminogen activator inhibitor 1 gene expression in murine liver by lipopo-lysaccharide. Cellular localization and role of endogenous tumor necrosis factor-a. Am. J. Pathol. 150, 579-590.
45. Feingold, K.R. and Grunfeld, C. (1987). Tumor necrosis factor-a stimulates hepatic lipogenesis in the rat in vivo. J. Clin. Invest. 80, 184-190.
46. Fernandez-Checa, J.C., Kaplowitz, N., Garcia-Ruiz, C., Colell, A., Miranda, M., Mari, M., Ardite, E., and Morales, A. (1997). GSH transport in mitochondria: defense against TNF-induced oxida-tive stress and alcohol-induced defect. Am. J. Physiol. 273, G7-G17.
47. Fibbi, G., Pucci, M., Grappone, C., Pellegrini, G., Salzano, R., Casi-ni, A., Milani, S., and Del Rosso, M. (1999). Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. Hepatology 29, 868-878.
48. Finkelstein, J.D. (1990). Methionine metabolism in mammals. J. Nutr. Biochem. 1, 228-237.
49. Fiorucci, S., Antonelli, E., Distrutti, E., Severino, B., Fiorentina, R., Baldoni, M., Caliendo, G., Santagada, V., Morelli, A., and Ciri-no, G. (2004). PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology 39, 365-375.
50. Forman, H.J. and Torres, M. (2001). Redox signaling in macro-phages. Mol. Aspects Med. 22, 189-216.
51. Fridovich, I. (1995). Superoxide radical and superoxide dismutases. Annu. Rev. Biochem. 64, 97-112.
52. Ganey, P.E., Luyendyk, J.P., Maddox, J.F., and Roth, R.A. (2004). Adverse hepatic drug reactions: inflammatory episodes as consequence and contributor. Chem. Biol. Interact. 150, 35-51.
53. Gatti, R.M., Alvarez, B., Vasquez-Vivar, J., Radi, R., and Augusto, O. (1998). Formation of spin trap adducts during the decomposition of peroxynitrite. Arch. Biochem. Biophys. 349, 36-46.
54. Gobejishvili, L., Barve, S., Joshi-Barve, S., Uriarte, S., Song, Z., and McClain, C. (2006). Chronic ethanol-mediated decrease in cAMP primes macrophages to enhanced LPS-inducible NF-kB activity and TNF expression: relevance to alcoholic liver disease. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G681-G688.
55. Gobejishvili, L., Barve, S., Joshi-Barve, S., and McClain, C. (2008). Enhanced PDE4B expression augments LPS-inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G718-G724.
56. Gogel, B.M., Goldstein, R.M., Kuhn, J.A., McCarty, T.M., Donahoe, A., and Glastad, K. (2000). Diagnostic evaluation of hepatocel-lular carcinoma in a cirrhotic liver. Oncology 14, 15-20.
57. Han, D., Ybanez, M.D., Ahmadi, S., Yeh, K., and Kaplowitz, N. (2009). Redox regulation of tumor necrosis factor signaling. Antioxid. Redox. Signal. 11, 2245-2263.
58. Hardardottir, I., Doerrler, W., Feingold, K.R., and Grunfeld, C. (1992). Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism. Biochem. Biophys. Res. Commun. 186, 237-243.
59. Hevia, H., Varela-Rey, M., Corrales, F.J., Berasain, C., Martinez-Chantar, M.L., Latasa, M.U., Lu, S.C., Mato, J.M., Garcia-Tre-vijano, E.R., and Avila, M.A. (2004). 59-Methylthioadenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes. Hepatology 39, 1088-1098.
60. Hill, D.B., Devalaraja, R., Joshi-Barve, S., Barve, S., and McClain, C.J. (1999). Antioxidants attenuate nuclear factor-kB activation and tumor necrosis factor-a production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro. Clin. Biochem. 32, 563-570.
61. Hodivala-Dilke, K.M., Reynolds, A.R., and Reynolds, L.E. (2003). Integrins in angiogenesis: multitalented molecules in a balancing act. Cell Tissue Res. 314, 131-144.
62. Hoek, J.B. and Pastorino, J.G. (2002). Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol 27, 63-68.
63. Hon, W.M., Lee, K.H., and Khoo, H.E. (2002). Nitric oxide in liver diseases: friend, foe, or just passerby? Ann. N.Y. Acad. Sci. 962, 275-295.
64. Hritz, I., Mandrekar, P., Velayudham, A., Catalano, D., Dolganiuc, A., Kodys, K., Kurt-Jones, E., and Szabo, G. (2008). The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88. Hepatology 48, 1224-1231.
65. Hu, K.Q., Yu, A.S., Tiyyagura, L., Redeker, A.G., and Reynolds, T.B. (2001). Hyperfibrinolytic activity in hospitalized cirrho-tic patients in a referral liver unit. Am. J. Gastroenterol. 96, 1581-1586.
66. Hultberg, B., Berglund, M., Andersson, A., and Frank, A. (1993). Elevated plasma homocysteine in alcoholics. Alcohol Clin. Exp. Res. 17, 687-689.
67. Iimuro, Y., Gallucci, R.M., Luster, M.I., Kono, H., and Thurman, R.G. (1997). Antibodies to tumor necrosis factor-a attenuate hepatic necrosis and inflammation due to chronic exposure to ethanol in the rat. Hepatology 26, 1530-1537.
68. Ji, C. and Kaplowitz, N. (2003). Betaine decreases hyperhomocys-teinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 124, 1488-1499.
69. Ji, S., Lemasters, J.J., and Thurman, R.G. (1982). Intralobular hepatic pyridine nucleotide fluorescence: evaluation of the hypothesis that chronic treatment with ethanol produces pericentral hypoxia. Proc. Natl. Acad. Sci. USA 80, 5415-5419.
70. Jones, D.P. (1985). The role of oxygen concentration in oxidative stress: hypoxic and hyperoxic models. In: Oxidative Stress, H. Sies, ed. (London, UK: Academic Press), pp. 151-195.
71. Joshi, P.C., Mehta, A., Jabber, W.S., Fan, X., and Guidot, D.M. (2009). Zinc deficiency mediates alcohol-induced alveolar epithelial and macrophage dysfunction in rats. Am. J. Respir. Cell Mol. Biol. 41, 207-216.
72. Kang, Y.J. and Zhou, Z. (2005). Zinc prevention and treatment of alcoholic liver disease. Mol. Aspects Med. 26, 391-404.
73. Kamata, H. and Hirata, H. (1999). Redox regulation of cellular signalling. Cell Signal. 11, 1-14.
74. Kim, Y.M., Kim, T.H., Chung, H.T., Talanian, R.V., Yin, X.M., and Billiar, T.R. (2000). Nitric oxide prevents tumor necrosis factor a-induced rat hepatocyte apoptosis by the interruption of mito-chondrial apoptotic signaling through S-nitrosylation of caspase-8. Hepatology 32, 770-778.
75. Kim, K.Y., Rhim, T., Choi, I., and Kim, S.S. (2001). N-Acetylcys-teine induces cell cycle arrest in hepatic stellate cells through its reducing activity. J. Biol. Chem. 276, 40591-40598.
76. Klassen, L.W., Tuma, D., and Sorrell, M.F. (1995). Immune mechanisms of alcohol-induced liver disease. Hepatology 22, 355-357.
77. Knecht, K.T., Thurman, R.G., and Mason, R.P. (1993). Role of supe-roxide and trace transition metals in the production of a-hydroxyethyl radical from ethanol by microsomes from alcohol dehydrogenase-deficient deer mice. Arch. Biochem. Biophys. 303, 339-348.
78. Kolev, K. and Machovich, R. (2003). Molecular and cellular modulation of fibrinolysis. Thromb. Haemost. 89, 610-621.
79. 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., et al. (1999). CYP2E1 is not involved in early alcohol-induced liver injury. Am. J. Physiol. 277, G1259-G1267.
80. Kono, H., Rusyn, I., Connor, H., Mason, R.P., and Thurman, R.G. (2000a). Allopurinol prevents early alcohol-induced liver injury in rats. J. Pharmacol. Exp. Ther. 293, 296-303.
81. Kono, H., Rusyn, I., Yin, M., Gabele, E., Yamashina, S., Dikalova, A., Kadiiska, M.B., Connor, H.D., Mason, R.P., Segal, B.H., et al. (2000b). NADPH oxidase-derived free radicals are key oxi-dants in alcohol-induced liver disease. J. Clin. Invest. 106, 867-872.
82. Kono, H., Arteel, G.E., Rusyn, I., Sies, H., and Thurman, R.G. (2001a). Ebselen prevents early alcohol-induced liver injury in rats. Free Radic. Biol. Med. 30, 403-411.
83. Kono, H., Rusyn, I., Uesugi, T., Yamashina, S., Connor, H.D., Dika-lova, A., Mason, R.P., and Thurman, R.G. (2001b). Diphenyle-neiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat. Am. J. Physiol. Gastroin-test. Liver Physiol. 280, G1005-G1012.
84. Kruithof, E.K. (1988). Plasminogen activator inhibitors-a review. Enzyme 40, 113-121.
85. Lambeth, J.D., Cheng, G., Arnold, R.S., and Edens, W.A. (2000). Novel homologs of gp91phox. Trends Biochem. Sci. 25, 459-461.
86. Leclercq, I.A., Farrell, G.C., Field, J., Bell, D.R., Gonzalez, F.J., and Robertson, G.R. (2001). The CYP2E1 knockout delivers another punch: first ASH, now NASH. Hepatology 33, 311-312.
87. Lieber, C.S. (1988). Metabolic effects of acetaldehyde. Biochem. Soc. Trans. 16, 241-247.
88. Lieber, C.S. (1997). Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta 257, 59-84.
89. Lieber, C.S. (2000). Alcohol: its metabolism and interaction with nutrients. Annu. Rev. Nutr. 20, 395-430.
90. Lieber, C.S. (2003). Relationships between nutrition, alcohol use, and liver disease. Alcohol Res. Health 27, 220-231.
91. Liu, H., Jones, B.E., Bradham, C., and Czaja, M.J. (2002). Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-a. Am. J. Physiol. Gas-trointest. Liver Physiol. 282, G257-G266.
92. Lu, S.C., Tsukamoto, H., and Mato, J.M. (2002). Role of abnormal methionine metabolism in alcoholic liver injury. Alcohol 27, 155-162.
93. Mammen, E.F. (1992). Coagulation abnormalities in liver disease. Hematol. Oncol. Clin. North Am. 6, 1247-1257.
94. Mandrekar, P. and Szabo, G. (2009). Signalling pathways in alcohol-induced liver inflammation. J. Hepatol. 50, 1258-1266.
95. Mann, R.E., Smart, R.G., and Govoni, R. (2003). The epidemiology of alcoholic liver disease. Alcohol Res. Health 27, 209-219.
96. Marques-Vidal, P., Cambou, J.P., Nicaud, V., Luc, G., Evans, A., Arveiler, D., Bingham, A., and Cambien, F. (1995). Cardiovascular risk factors and alcohol consumption in France and Northern Ireland. Atherosclerosis 115, 225-232.
97. Marra, F., Grandaliano, G., Valente, A.J., and Abboud, H.E. (1995). Thrombin stimulates proliferation of liver fat-storing cells and expression of monocyte chemotactic protein-1: potential role in liver injury. Hepatology 22, 780-787.
98. Mato, J.M., Corrales, F.J., Lu, S.C., and Avila, M.A. (2002). S-Adenosylmethionine: a control switch that regulates liver function. FASEB J. 16, 15-26.
99. McClain, C.J. and Cohen, D.A. (1989). Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepato-logy 9, 349-351.
100. McKim, S.E., Gabele, E., Isayama, F., Lambert, J.C., Tucker, L.M., Wheeler, M.D., Connor, H.D., Mason, R.P., Doll, M.A., Hein, D.W., et al. (2003). Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice. Gas-troenterology 125, 1834-1844.
101. McVicker, B.L., Tuma, D.J., and Casey, C.A. (2007). Effect of eth-anol on pro-apoptotic mechanisms in polarized hepatic cells. World J. Gastroenterol. 13, 4960-4966.
102. Monroe, D.M. and Hoffman, M. (2009). The coagulation cascade in cirrhosis. Clin. Liver Dis. 13, 1-9.
103. Mukamal, K.J., Jadhav, P.P., D'Agostino, R.B., Massaro, J.M., Mitt-leman, M.A., Lipinska, I., Sutherland, P.A., Matheney, T., Levy, D., Wilson, P.W., et al. (2001). Alcohol consumption and hemo-static factors: analysis of the Framingham Offspring cohort. Circulation 104, 1367-1373.
104. Nachiappan, V., Curtiss, D., Corkey, B.E., and Kilpatrick, L. (1994). Cytokines inhibit fatty acid oxidation in isolated rat hepatocytes: synergy among TNF, IL-6, and IL-1. Shock 1, 123-129.
105. Nagy, L.E. (2004a). Molecular aspects of alcohol metabolism: transcription factors involved in early ethanol-induced liver injury. Annu. Rev. Nutr. 24, 55-78.
106. Nagy, L.E. (2004b). Stabilization of tumor necrosis factor-a mRNA in macrophages in response to chronic ethanol exposure. Alcohol 33, 229-233.
107. Nanji, A.A., Greenberg, S.S., Tahan, S.R., Fogt, F., Loscalzo, J., Sadrzadeh, S.M., Xie, J., and Stamler, J.S. (1995). Nitric oxide production in experimental alcoholic liver disease in the rat: role in protection from injury. Gastroenterology 109, 899-907.
108. Nanji, A.A., Jokelainen, K., Lau, G.K., Rahemtulla, A., Tipoe, G.L., Polavarapu, R., and Lalani, E. (2001). Arginine reverses ethanol-induced inflammatory and fibrotic changes in liver despite continued ethanol administration. J. Pharmacol. Exp. Ther. 299, 832-839. (Pubitemid 33104949)
109. Navasa, M., Gordon, D.A., Hariharan, N., Jamil, H., Shigenaga, J.K., Moser, A., Fiers, W., Pollock, A., Grunfeld, C., and Fein-gold, K.R. (1998). Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines. J. Lipid Res. 39, 1220-1230. (Pubitemid 28270085)
110. Naveau, S., Chollet-Martin, S., Dharancy, S., Mathurin, P., Jouet, P., Piquet, M.A., Davion, T., Oberti, F., Broet, P., and Emilie, D. (2004). A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology 39, 1390-1397.
111. Niemela, O. (2001). Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radic. Biol. Med. 31, 1533-1538.
112. Northup, P.G., Sundaram, V., Fallon, M.B., Reddy, K.R., Balogun, R.A., Sanyal, A.J., Anstee, Q.M., Hoffman, M.R., Ikura, Y., and Caldwell, S.H. (2008). Hypercoagulation and thrombophilia in liver disease. J. Thromb. Haemost. 6, 2-9.
113. Oshita, M., Takei, Y., Kawano, S., Hijioka, T., Masuda, E., Goto, M., Nishimura, Y., Nagai, H., Iio, S., Tsuji, S., et al. (1994). Endogenous nitric oxide attenuates ethanol-induced perturbation of hepatic circulation in the isolated perfused rat liver. Hepatology 20, 961-965.
114. Pearson, J.M., Schultze, A.E., Schwartz, K.A., Scott, M.A., Davis, J.M., and Roth, R.A. (1996). The thrombin inhibitor, hirudin, attenuates lipopolysaccharide-induced liver injury in the rat. J. Pharmacol. Exp. Ther. 278, 378-383.
115. Pessayre, D., Mansouri, A., and Fromenty, B. (2002). Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G193-G199.
116. Poli, G. (2000). Pathogenesis of liver fibrosis: role of oxidative stress. Mol. Aspects Med. 21, 49-98.
117. Powell, W.J. Jr. and Klatskin, G. (1968). Duration of survival in patients with Laennec's cirrhosis. Influence of alcohol withdrawal, and possible effects of recent changes in general management of the disease. Am. J. Med. 44, 406-420.
118. Rai, R.M., Lee, F.Y., Rosen, A., Yang, S.Q., Lin, H.Z., Koteish, A., Liew, F.Y., Zaragoza, C., Lowenstein, C., and Diehl, A.M. (1998). Impaired liver regeneration in inducible nitric oxide syn-thase deficient mice. Proc. Natl. Acad. Sci. USA 95, 13829-13834.
119. Rawson, R.B. (2003). The SREBP pathway-insights from Insigs and insects. Nat. Rev. Mol. Cell Biol. 4, 631-640.
120. Reeves, H.L., Dack, C.L., Peak, M., Burt, A.D., and Day, C.P. (2000). Stress-activated protein kinases in the activation of rat hepatic stellate cells in culture. J. Hepatol. 32, 465-472.
121. Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teera-wattananon, Y., and Patra, J. (2009). Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373, 2223-2233.
122. Reinehr, R., Becker, S., Eberle, A., Grether-Beck, S., and Häussin-ger, D. (2005a). Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. J. Biol. Chem. 280, 27179-27194.
123. Reinehr, R., Becker, S., Keitel, V., Eberle, A., Grether-Beck, S., and Häussinger, D. (2005b). Bile salt-induced apoptosis involves NADPH oxidase isoform activation. Gastroenterology 129, 2009-2031.
124. Roman, J., Colell, A., Blasco, C., Caballeria, J., Pares, A., Rodes, J., and Fernandez-Checa, J.C. (1999). Differential role of ethanol and acetaldehyde in the induction of oxidative stress in HEP G2 cells: effect on transcription factors AP-1 and NF-kB. Hepatology 30, 1473-1480.
125. Rubbo, H., Radi, R., Anselmi, D., Kirk, M., Barnes, S., Butler, J., Eiserich, J.P., and Freeman, B.A. (2000). Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/a-tocopherol than a-tocopherol/ascorbate. J. Biol. Chem. 275, 10812-10818.
126. Ruderman, N.B., Xu, X.J., Nelson, L., Cacicedo, J.M., Saha, A.K., Lan, F., and Ido, Y. (2010). AMPK and SIRT1: a long-standing partnership? Am. J. Physiol. Endocrinol. Metab. 298, E751-E760.
127. Shan, X., Aw, T.Y., Shapira, R., and Jones, D.P. (1989). Oxygen dependence of glutathione synthesis in hepatocytes. Toxicol. Appl. Pharmacol. 101, 261-270.
128. Shaw, S., Jayatilleke, E., Ross, W.A., Gordon, E.R., and Lieber, S. (1981). Ethanol-induced lipid peroxidation: potentiation by long-term alcohol feeding and attenuation by methionine. J. Lab. Clin. Med. 98, 417-424.
129. Shaw, S., Jayatilleke, E., and Lieber, C.S. (1988). Lipid peroxidation as a mechanism of alcoholic liver injury: role of iron mobilization and microsomal induction. Alcohol 5, 135-140.
130. Shea-Budgell, M., Dojka, M., Nimmo, M., Lee, D., and Xu, Z. (2006). Marginal zinc deficiency increased the susceptibility to acute lipopolysaccharide-induced liver injury in rats. Exp. Biol. Med. 231, 553-558.
131. Sies, H. (1986). Biochemistry of oxidative stress. Angew. Chem. Int. Ed. 25, 1058-1071.
132. 2 receptor. Biochim. Biophys. Acta 1743, 205-213.
133. Song, Z., Zhou, Z., Song, M., Uriarte, S., Chen, T., Deaciuc, I., and McClain, C.J. (2007). Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: possible involvement of mitochondrial S-adenosylmethionine transport. Biochem. Pharmacol. 74, 521-531.
134. Sorensen, T.I., Orholm, M., Bentsen, K.D., Hoybye, G., Eghoje, K., and Christoffersen, P. (1984). Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis. Lancet 2, 241-244.
135. Spencer, S., Rubin, K.P., and Lieber, C.S. (1983). Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease: evidence of lipid peroxidation. Dig. Dis. Sci. 28, 585-589.
136. Suzuki, Y.J., Forman, H.J., and Sevanian, A. (1997). Oxidants as stimulators of signal transduction. Free Radic. Biol. Med. 22, 269-285.
137. Szabo, G. and Bala, S. (2010). Alcoholic liver disease and the gut-liver axis. World J. Gastroenterol. 16, 1321-1329.
138. Taieb, J., Mathurin, P., Poynard, T., Gougerot-Pocidalo, M.A., and Chollet-Martin, S. (1998). Raised plasma soluble Fas and Fas-ligand in alcoholic liver disease. Lancet 351, 1930-1931.
139. Takahashi, M., Saito, H., Higashimoto, M., and Hibi, T. (2007). Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP-1: a pilot study. Hepa-tol. Res. 37, 405-409.
140. Teli, M.R., Day, C.P., Burt, A.D., Bennett, M.K., and James, O.F. (1995). Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet 346, 987-990.
141. Thurman, R.G. (1998). Mechanisms of hepatic toxicity. II. Alcoholic liver injury involves activation of Kupffer cells by endo-toxin. Am. J. Physiol. 275, G605-G611.
142. Tran-Thang, C., Fasel-Felley, J., Pralong, G., Hofstetter, J.R., Bach-mann, F., and Kruithof, E.K. (1989). Plasminogen activators and plasminogen activator inhibitors in liver deficiencies caused by chronic alcoholism or infectious hepatitis. Thromb. Haemost. 62, 651-653.
143. Tribble, D.L. and Jones, D.P. (1990). Oxygen dependence of oxi-dative stress: rate of NADPH supply for maintaining the GSH pool during hypoxia. Biochem. Pharmacol. 39, 729-736.
144. Veal, N., Hsieh, C.L., Xiong, S., Mato, J.M., Lu, S., and Tsukamoto, H. (2004). Inhibition of lipopolysaccharide-stimulated TNF-a promoter activity by S-adenosylmethionine and 59-methyl-thioadenosine. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G352-G362.
145. Violi, F., Ferro, D., Basili, S., Quintarelli, C., Saliola, M., Alessan-dri, C., Cordova, C., and Balsano, F. (1992). Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis. Hepatology 15, 672-676.
146. Wheeler, M.D. and Thurman, R.G. (2003). Up-regulation of CD14 in liver caused by acute ethanol involves oxidant-dependent AP-1 pathway. J. Biol. Chem. 278, 8435-8441.
147. Wheeler, M.D., Kono, H., Yin, M., Rusyn, I., Froh, M., Connor, H.D., Mason, R.P., Samulski, R.J., and Thurman, R.G. (2001a). Delivery of Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology 120, 1241-1250. (Pubitemid 32248748)
148. Wheeler, M.D., Nakagami, M., Bradford, B.U., Uesugi, T., Mason, R.P., Connor, H.D., Dikalova, A., Kadiiska, M., and Thurman, R.G. (2001b). Overexpression of manganese superoxide dismu-tase prevents alcohol-induced liver injury in the rat. J. Biol. Chem. 276, 36664-36672.
149. Wiest, R. and Groszmann, R.J. (2002). The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 35, 478-491.
150. Yang, S.Q., Lin, H.Z., Lane, M.D., Clemens, M., and Diehl, A.M. (1997). Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc. Natl. Acad. Sci. USA 94, 2557-2562.
151. Yin, M., Wheeler, M.D., Kono, H., Bradford, B.U., Gallucci, R.M., Luster, M.I., and Thurman, R.G. (1999). Essential role of tumor necrosis factor a in alcohol-induced liver injury. Gastroenterology 117, 942-952.
152. Yin, M., Bradford, B.U., Wheeler, M.D., Uesugi, T., Froh, M., Goyert, S.M., and Thurman, R.G. (2001a). Reduced early alcohol-induced liver injury in cd14-deficient mice. J. Immunol. 166, 4737-4742.
153. Yin, M., Gabele, E., Wheeler, M.D., Connor, H., Bradford, B.U., Dikalova, A., Rusyn, I., Mason, R., and Thurman, R.G. (2001b). Alcohol-induced free radicals in mice: direct toxicants or signaling molecules? Hepatology 34, 935-942.
154. You, M. and Crabb, D.W. (2004). Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver. Am. J. Physiol Gastrointest. Liver Physiol. 287, G1-G6.
155. You, M., Cao, Q., Liang, X., Ajmo, J.M., and Ness, G.C. (2008). Mammalian sirtuin 1 is involved in the protective action of dietary saturated fat against alcoholic fatty liver in mice. J. Nutr. 138, 497-501.
156. Yuki, T. and Thurman, R.G. (1980). The swift increase in alcohol metabolism: time course for the increase in hepatic oxygen uptake and the involvement of glycolysis. Biochem. J. 186, 119-126.
157. Zania, P., Papaconstantinou, M., Flordellis, C.S., Maragoudakis, M.E., and Tsopanoglou, N.E. (2008). Thrombin mediates mito-genesis and survival of human endothelial cells through distinct mechanisms. Am. J. Physiol Cell Physiol. 294, C1215-C1226.
158. Zhong, W., McClain, C.J., Cave, M., Kang, Y.J., and Zhou, Z. (2010). The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G625-G633.
159. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174.
160. Zhou, Z., Kang, X., Jiang, Y., Song, Z., Feng, W., McClain, C.J., and Kang, Y.J. (2007). Preservation of hepatocyte nuclear factor-4a is associated with zinc protection against TNF-a hepatotox-icity in mice. Exp. Biol. Med. (Maywood) 232, 622-628.
161. Zhou, H.F., Chan, H.W., Wickline, S.A., Lanza, G.M., and Pham, C.T. (2009). avb3-targeted nanotherapy suppresses inflammatory arthritis in mice. FASEB J. 23, 2978-2985.