ER stress: Can the liver cope?ss

Journal of Hepatology

Volumn 45, Issue 2, 2006, Pages 321-333

  Ji, Cheng ^a   Kaplowitz, Neil ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

1 AT deficiency; Alcoholic liver disease; HBV; HCV; Hyperhomocysteinemia; Insulin resistance; Ischemia; NASH; Steatosis

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; MEMBRANE PROTEIN; PHOSPHOTRANSFERASE; PKR LIKE ENDOPLASMIC RETICULUM KINASE; PROTEIN IRE1; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ADAPTATION; ALCOHOL ABUSE; ALCOHOLISM; ALPHA 1 ANTITRYPSIN DEFICIENCY; CELL DEATH; CELL FUNCTION; DIABETIC OBESITY; DOWN REGULATION; ENDOPLASMIC RETICULUM; FATTY LIVER; GENE MUTATION; GENETIC CODE; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HYPERHOMOCYSTEINEMIA; INSULIN SYNTHESIS; LIVER CELL; LIVER DISEASE; LIVER INJURY; LIVER ISCHEMIA; LIVER PERFUSION; LIVER PROTECTION; LIVER TOXICITY; METABOLIC DISORDER; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN METABOLISM; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; STRESS; TRANSCRIPTION REGULATION; TRANSLATION INITIATION; VIRUS CARRIER;

ANIMALS; ENDOPLASMIC RETICULUM; HEPATOCYTES; HUMANS; LIVER DISEASES; OXIDATIVE STRESS;

EID: 33745890321     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2006.06.004     Document Type: Review

References (151)

1. Lindquist S. The heat-shock response. Annu Rev Biochem 55 (1986) 1151-1191
2. Ma Y., and Hendershot L.M. The unfolding tale of the unfolded protein response. Cell 107 (2001) 827-830
3. Wiest D.L., Burkhardt J.K., Hester S., Hortsch M., Meyer D.I., and Argon Y. Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol 110 (1990) 1501-1511
4. Iwakoshi N.N., Lee A.H., Vallabhajosyula P., Otipoby K.L., Rajewsky K., and Glimcher L.H. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol 4 (2003) 321-329
5. Gunn K.E., Gifford N.M., Mori K., and Brewer J.W. A role for the unfolded protein response in optimizing antibody secretion. Mol Immunol 41 (2004) 919-927
6. Kaufman R.J. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13 (1999) 1211-1233
7. Mori K. Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101 (2000) 451-454
8. Patil C., and Walter P. Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol 13 (2001) 349-355
9. Harding H.P., Calfon M., Urano F., Novoa I., and Ron D. Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol 18 (2002) 575-599
10. Xu C., Bailly-Maitre B., and Reed J.C. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115 (2005) 2656-2664
11. Zhang K., and Kaufman R.J. The unfolded protein response: a stress signaling pathway critical for health and disease. Neurology 66 (2006) S102-S109
12. Lee A.S., Delegeane A.M., Baker V., and Chow P.C. Transcriptional regulation of two genes specifically induced by glucose starvation in a hamster mutant fibroblast cell line. J Biol Chem 258 (1983) 597-603
13. Munro S., and Pelham H.R. An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46 (1986) 291-300
14. Tirasophon W., Welihinda A.A., and Kaufman R.J. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev 12 (1998) 1812-1824
15. Wang X.Z., Harding H.P., Zhang Y., Jolicoeur E.M., Kuroda M., and Ron D. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 17 (1998) 5708-5717
16. Haze K., Yoshida H., Yanagi H., Yura T., and Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 10 (1999) 3787-3799
17. Shi Y., Vattem K.M., Sood R., An J., Liang J., Stramm L., et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PERK, involved in translational control. Mol Cell Biol 18 (1998) 7499-7509
18. Dorner A.J., Wasley L.C., and Kaufman R.J. Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells. Eur Mol Biol Org J 11 (1992) 1563-1571
19. Bertolotti A., Zhang Y., Hendershot L.M., Harding H.P., and Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2 (2000) 326-332
20. Shen J., Chen X., Hendershot L., and Prywes R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3 (2002) 99-111
21. Liu C.Y., Wong H.N., Schauerte J.A., and Kaufman R.J. The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain. J Biol Chem 277 (2002) 18346-18356
22. Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P., et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415 (2002) 92-96
23. Hetz C., Bernasconi P., Fisher J., Lee A.H., Bassik M.C., Antonsson B., et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 312 (2006) 572-576
24. Lee A.H., Iwakoshi N.N., and Glimcher L.H. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23 (2003) 7448-7459
25. Brown M.S., Ye J., Rawson R.B., and Goldstein J.L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 1 (2000) 391-398
26. Ye J., Rawson R.B., Komuro R., Chen X., Dave U.P., Prywes R., et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6 (2000) 1355-1364
27. Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., et al. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol Cell Biol 20 (2000) 6755-6767
28. Li M., Baumeister P., Roy B., Phan T., Foti D., Luo S., et al. ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1. Mol Cell Biol 20 (2000) 5096-5106
29. Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., et al. Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response. Mol Cell Biol 21 (2001) 1239-1248
30. Kokame K., Kato H., and Miyata T. Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response. J Biol Chem 276 (2001) 9199-9205
31. Parker R., Phan T., Baumeister P., Roy B., Cheriyath V., Roy A.L., et al. Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6. Mol Cell Biol 21 (2001) 3220-3233
32. Ma Y., and Hendershot L.M. Herp is dually regulated by both the endoplasmic reticulum stress-specific branch of the unfolded protein response and a branch that is shared with other cellular stress pathways. J Biol Chem 279 (2004) 13792-13799
33. Yamamoto K., Yoshida H., Kokame K., Kaufman R.J., and Mori K. Differential contributions of ATF6 and XBP1 to the activation of endoplasmic reticulum stress-responsive cis-acting elements ERSE, UPRE and ERSE-II. J Biochem (Tokyo) 136 (2004) 343-350
34. Marciniak S.J., Yun C.Y., Oyadomari S., Novoa I., Zhang Y., Jungreis R., et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev 18 (2004) 3066-3077
35. Werner E.D., Brodsky J.L., and McCracken A.A. Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate. Proc Natl Acad Sci USA 93 (1996) 13797-13801
36. Dorner A.J., Wasley L.C., and Kaufman R.J. Protein dissociation from GRP78 and secretion are blocked by depletion of cellular ATP levels. Proc Natl Acad Sci USA 87 (1990) 7429-7432
37. Leppa S., and Bohmann D. Diverse functions of JNK signaling and c-Jun in stress response and apoptosis. Oncogene 18 (1999) 6158-6162
38. Yoneda T., Imaizumi K., Oono K., et al. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276 (2001) 13935-13940
39. Nishitoh H., Matsuzawa A., Tobiume K., et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 16 (2002) 1345-1355
40. Nakagawa T., Zhu H., Morishima N., et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403 (2000) 98-103
41. Morishima N., Nakanishi K., Takenouchi H., Shibata T., and Yasuhiko Y. An ER stress-specific caspase cascade in apoptosis: cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem 3 (2002) 3
42. Boyce M., and Yuan J. Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13 (2006) 363-373
43. Ma Y., Brewer J.W., Diehl J.A., and Hendershot L.M. Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response. J Mol Biol 318 (2002) 1351-1365
44. Harding H.P., Zhang Y., Zeng H., Novoa I., Lu P.D., Calfon M., et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 11 (2003) 619-633
45. Pahl H.L., and Baeuerle P.A. The ER-overload response: activation of NF-kappa B. Trends Biochem Sci 22 (1997) 63-67
46. Buytaert E., Callewaert G., Hendrickx N., Scorrano L., Hartmann D., Missiaen L., et al. Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy. FASEB J 20 (2006) 756-758
47. Omori Y., Imai J., Watanabe M., Komatsu T., Suzuki Y., Kataoka K., et al. CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression. Nucleic Acids Res (2001) 2154-2162
48. Yoo J.Y., and Desiderio S. Innate and acquired immunity intersect in a global view of the acute-phase response. Proc Natl Acad Sci USA (2003) 1157-1162
49. Zhang K., Shen X., Wu J., Sakaki K., Saunders T., Rutkowski D.T., et al. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 124 (2006) 587-599
50. Sakai J., Nohturfft A., Cheng D., Ho Y.K., Brown M.S., and Goldstein J.L. Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein. J Biol Chem 272 (1997) 20213-20221
51. Goldstein J.L., DeBose-Boyd R.A., and Brown M.S. Protein sensors for membrane sterols. Cell 124 (2006) 35-46
52. Brown M.S., and Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89 (1997) 331-340
53. Ron D., and Oyadomari S. Lipid phase perturbations and the unfolded protein response. Dev Cell 7 (2004) 287-288
54. Werstuck G.H., Lentz S.R., Dayal S., Hossain G.S., Sood S.K., Shi Y.Y., et al. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest 107 (2001) 1263-1273
55. Ji C., and Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 124 (2003) 1488-1499
56. Hansson G.K. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352 (2005) 1685-1695
57. Tsukiyama-Kohara K., Iizuka N., Kohara M., and Nomoto A. Internal ribosome entry site within hepatitis C virus RNA. J Virol (1992) 1476-1483
58. Wang C., Sarnow P., and Siddiqui A. Translation of human hepatitis C virus RNA is cultured cells is mediated by an internal ribosome-binding mechanism. J Virol (1993) 3338-3344
59. Grakoui A., Wychowski C., Lin C., Feinstone S.M., and Rice C.M. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol (1993) 1385-1395
60. Gong G., Waris G., Tanveer R., and Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-κB. Proc Natl Acad Sci USA (2001) 9599-9604
61. Tardif K.D., Mori K., and Siddiqui A. Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway. J Virol (2002) 7453-7459
62. Egger D., Wölk B., Gosert R., Bianchi L., Blum H.E., Moradpour D., et al. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol (2002) 5974-5984
63. Zheng Y., Gao B., Ye L., Kong L., Jing W., Yang X., et al. Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response. J Microbiol 43 (2005) 529-536
64. Tardif K.D., Mori K., Kaufman R.J., and Siddiqui A. Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response. J Biol Chem (2004) 17158-17164
65. Hosokawa N., Wada I., Hasegawa K., Yorihuzi T., Tremblay L.O., Herscovics A., et al. A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO Rep 2 (2001) 415-422
66. Tardif K.D., Waris G., and Siddiqui A. Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol 13 (2005) 159-163
67. Michael Jr. J., Gale Marcus J., Korth Norina M., Tang Seng-Lai T., Deborah A., Hopkins Thomas E., et al. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural protein 5A. Virology (1997) 217-227
68. Taylor D.R., Shi S.T., Romano P.R., Barber G.N., and Lai M.M. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science (1999) 107-110
69. He B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ 13 (2006) 393-403
70. Harding H.P., Yuhong Z., and Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature (1999) 271-274
71. Prostko C.R., Dholakia J.N., Brostrom M.A., and Brostrom C.O. Activation of the double-stranded RNA-regulated protein kinase by depletion of endoplasmic reticular calcium stores. J Biol Chem (1995) 6211-6215
72. Pavio N., Romano P.R., Graczyk T.M., Feinstone S.M., and Taylor D.R. Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK. J Virol 77 (2003) 3578-3585
73. Chan S.W., and Egan P.A. Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response. FASEB J 19 (2005) 1510-1512
74. Liberman E., Fong Y.L., Selby M.J., Choo Q.L., Cousens L., Houghton M., et al. Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope protein. J Virol 73 (1999) 3718-3722
75. Benali-Furet N.L., Chami M., Houel L., De Giorgi F., Vernejoul F., Lagorce D., et al. Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene 24 (2005) 4921-4933
76. Bowman T., Garcia R., Turkson J., and Jove R. STATs in oncogenesis. Oncogene 19 (2000) 2474-2488
77. Waris G., Turkson J., Hassanein T., and Siddiqui A. Hepatitis C virus (HCV) constitutively activates STAT-3 via oxidative stress:role of STAT-3 in HCV replication. J Virol 79 (2005) 1569-1580
78. Tardif K.D., and Siddiqui A. Cell surface expression of major histocompatibility complex class I molecules is reduced in hepatitis C virus subgenomic replicon-expressing cells. J Virol 77 (2003) 11644-11650
79. McKiernan S.M., Hagan R., Curry M., McDonald G.S., Kelly A., Nolan N., et al. Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source. Hepatology 40 (2004) 108-114
80. Ganem D., and Prince A.M. Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 350 (2004) 1118-1129
81. Xu Z., Jensen G., and Yen T.S. Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. J Virol 71 (1997) 7387-7392
82. Chua P.K., Wang R.Y., Lin M.H., Masuda T., Suk F.M., and Shih C. Reduced secretion of virions and hepatitis B virus (HBV) surface antigen of a naturally occurring HBV variant correlates with the accumulation of the small S envelope protein in the endoplasmic reticulum and Golgi apparatus. J Virol 79 (2005) 13483-13496
83. Chisari F.V., Filippi P., McLachlan A., Milich D.R., Riggs M., and Lee S. Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice. J Virol 60 (1986) 880-887
84. Chisari F.V., Filippi P., Buras J., McLachlan A., Popper H., Pinkert C.A., et al. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci USA 84 (1987) 6909-6913
85. Gilles P.N., Guerrette D.L., Ulevitch R.J., Schreiber R.D., and Chisari F.V. HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. Hepatology 16 (1992) 655-663
86. Wang H.C., Chang W.T., Chang W.W., Wu H.C., Huang W., Lei H.Y., et al. Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes. Hepatology 41 (2005) 761-770
87. Hsieh Y.H., Su I.J., Wang H.C., Chang W.W., Lei H.Y., Lai M.D., et al. Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis 25 (2004) 2023-2032
88. Hung J.H., Su I.J., Lei H.Y., Wang H.C., Lin W.C., Chang W.T., et al. Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-kappaB and pp38 mitogen-activated protein kinase. J Biol Chem 279 (2004) 46384-46392
89. Hotamisligil G.S. Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes 54 (2005) S73-S78
90. Itoh N., and Okamoto H. Translational control of proinsulin synthesis by glucose. Nature 283 (1980) 100-102
91. Lipson K.L., Fonseca S.G., and Urano F. Endoplasmic reticulum stress-induced apoptosis and auto-immunity in diabetes. Curr Mol Med 6 (2006) 71-77
92. Day C.P., and James O. Steatohepatitis: a tale of two "hits"?. Gastroenterology 114 (1998) 842-845
93. Listenberger L.L., Ory D.S., and Schaffer J.E. Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem 276 (2001) 14890-14895
94. Wang D., Wei Y., and Pagliassotti M.J. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology 147 (2006) 943-951
95. Pouyssegur J., Shiu R., and Pastan I. Induction of two transformation-sensitive membrane polypeptides in normal fibroblasts by a block in glycoprotein synthesis or glucose deprivation. Cell 11 (1977) 941-947
96. Wang D., Wei Y., Schmoll D., Maclean K.N., and Pagliassotti M.J. Endoplasmic reticulum stress increases glucose-6-phosphatase and glucose cycling in liver cells. Endocrinology 147 (2006) 350-358
97. Scheuner D., Song B., McEwen E., Liu C., Laybutt R., Gillespie P., et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7 (2001) 1165-1176
98. Harding H.P., Zeng H., Zhang Y., Jungries R., Chung P., Plesken H., et al. Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival. Mol Cell 7 (2001) 1153-1163
99. Delepine M., Nicolino M., Barrett T., Golamaully M., MarkLathrop G., and Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with wolcott-rallison syndrome. Nat Genet 25 (2000) 406-409
100. Araki E., Oyadomari S., and Mori M. Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus. Exp Biol Med (Maywood) 228 (2003) 1213-1217
101. Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306 (2004) 457-461
102. Urano F., Wang X., Bertolotti A., Zhang Y., Chung P., Harding H.P., et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science (2000) 664-666
103. Tamatani M., Matsuyama T., Yamaguchi A., Mitsuda N., Tsukamoto Y., Taniguchi M., et al. ORP150 protects against hypoxia/ischemia-induced neuronal death. Nat Med 7 (2001) 317-323
104. Nakatani Y., Kaneto H., Hatazaki M., Yoshiuchi K., Kawamori D., Sakamoto K., et al. Increased stress protein ORP150 autoantibody production in Type 1 diabetic patients. Diabet Med 23 (2006) 216-219
105. Tsukamoto Y., Kuwabara K., Hirota S., et al. 150-kDa oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein. J Clin Invest 98 (1996) 1930-1941
106. Teckman J.H., and Lindblad D. Alpha-1-antitrypsin deficiency: diagnosis, pathophysiology, and management. Curr Gastroenterol Rep 8 (2006) 14-20
107. Lawless M.W., Greene C.M., Mulgrew A., Taggart C.C., O'Neill S.J., and McElvaney N.G. Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. J Immunol 172 (2004) 5722-5726
108. Teckman J.H., An J.K., Loethen S., and Perlmutter D.H. Fasting in alpha1-antitrypsin deficient liver: constitutive activation of autophagy. Am J Physiol Gastrointest Liver Physiol 283 (2002) G1156-G1165
109. Papp E., Szaraz1 P., Korcsmaros T., and Csermely P. Changes of endoplasmic reticulum chaperone complexes, redox state, and impaired protein disulfide reductase activity in misfolding {ralpha}1-antitrypsin transgenic mice. FASEB J (2006)
110. Hidvegi T., Schmidt B.Z., Hale P., and Perlmutter D.H. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J Biol Chem 280 (2005) 39002-39015
111. Sakon M., Ariyoshi H., Umeshita K., and Monden M. Ischemia-reperfusion injury of the liver with special reference to calcium-dependent mechanisms. Surg Today 32 (2002) 1-12
112. Li C., and Jackson R.M. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282 (2002) C227-C241
113. Tilg H., Ceska M., Vogel W., Herold M., Margreiter R., and Huber C. Interleukin-8 serum concentrations after liver transplantation. Transplantation 53 (1992) 800-803
114. Emadali A., Nguyen D.T., Rochon C., Tzimas G.N., Metrakos P.P., and Chevet E. Distinct endoplasmic reticulum stress responses are triggered during human liver transplantation. J Pathol 207 (2005) 111-118
115. Vilatoba M., Eckstein C., Bilbao G., Smyth C.A., Jenkins S., Thompson J.A., et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis. Surgery 138 (2005) 342-351
116. Bailly-Maitre B., Fondevila C., Kaldas F., Droin N., Luciano F., Ricci J.E., et al. Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Proc Natl Acad Sci USA (2006)
117. Chae H.J., Kim H.R., Xu C., Bailly-Maitre B., Krajewska M., Krajewski S., et al. BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. Mol Cell 15 (2004) 355-366
118. Lieber C.S. Pathogenesis and treatment of alcoholic liver disease: progress over the last 50 years. Rocz Akad Med Bialymst 50 (2005) 7-20
119. Ji C., and Kaplowitz N. Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury. World J Gastroenterol 10 (2004) 1699-1708
120. Coll O., Colell A., Garcia-Ruiz C., Kaplowitz N., and Fernandez-Checa J.C. Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology 38 (2003) 692-702
121. Esfandiari F., Villanueva J.A., Wong D.H., French S.W., and Halsted C.H. Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol 289 (2005) G54-G63
122. Bleich S., Bleich K., Kropp S., Bittermann H.J., Degner D., Sperling W., et al. Moderate alcohol consumption in social drinkers raises plasma homocysteine levels: a contradiction to the 'French Paradox'?. Alcohol Alcohol 36 (2001) 189-192
123. Carmel R., and James S.J. Alcohol abuse: an important cause of severe hyperhomocysteinemia. Nutr Rev 60 (2002) 215-221
124. Sakuta H., and Suzuki T. Alcohol consumption and plasma homocysteine. Alcohol 37 (2005) 73-77
125. Bleich S., Bandelow B., Javaheripour K., Muller A., Degner D., Wilhelm J., et al. Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism. Neurosci Lett 335 (2003) 179-182
126. Stickel F., Choi S.W., Kim Y.I., Bagley P.J., Seitz H.K., Russell R.M., et al. Effect of chronic alcohol consumption on total plasma homocysteine level in rats. Alcohol Clin Exp Res 24 (2000) 259-264
127. Ji C., Mehrian-Shai R., Chan C., Hsu Y.H., and Kaplowitz N. Role of CHOP in hepatic apoptosis in the murine model of intragastric ethanol feeding. Alcohol Clin Exp Res 29 (2005) 1496-1503
128. Ji C., Deng Q., and Kaplowitz N. Role of TNF-alpha in ethanol-induced hyperhomocysteinemia and murine alcoholic liver injury. Hepatology 40 (2004) 442-451
129. Kenyon S.H., Nicolaou A., and Gibbons W.A. The effect of ethanol and its metabolites upon methionine synthase activity in vitro. Alcohol 15 (1998) 305-309
130. Barak A.J., Beckenhauer H.C., and Tuma D.J. Betaine, ethanol, and the liver: a review. Alcohol 13 (1996) 395-398
131. Halsted C.H., Villanueva J., Chandler C.J., Stabler S.P., Allen R.H., Muskhelishvili L., et al. Ethanol feeding of micropigs alters methionine metabolism and increases hepatocellular apoptosis and proliferation. Hepatology 23 (1996) 497-505
132. Halsted C.H., Villanueva J.A., Devlin A.M., Niemela O., Parkkila S., Garrow T.A., et al. Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. Proc Natl Acad Sci USA 99 (2002) 10072-10077
133. Villanueva J.A., and Halsted C.H. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Hepatology 39 (2004) 1303-1310
134. Tuma D.J., Keefer R.C., Beckenhauer H.C., and Barak A.J. Effect of ethanol on uptake of choline by the isolated perfused rat liver. Biochim Biophys Acta 218 (1970) 141-147
135. Thompson J.A., and Reitz R.C. Studies of the acute and chronic effects of ethanol ingestion on choline oxidation. Ann N Y Acad Sci 273 (1976) 194-204
136. Jakubowski H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. FASEB J 13 (1999) 2277-2283
137. Outinen P.A., Sood S.K., Liaw P.C., Sarge K.D., Maeda N., Hirsh J., et al. Characterization of the stress-inducing effects of homocysteine. Biochem J 332 (1998) 213-221
138. Outinen P.A., Sood S.K., Pfeifer S.I., Pamidi S., Podor T.J., Li J., et al. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood 94 (1999) 959-967
139. Zhang C., Cai Y., Adachi M.T., Oshiro S., Aso T., Kaufman R.J., et al. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem 276 (2001) 35867-35874
140. Agarwala K.L., Kokame K., Kato H., and Miyata T. Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein. Biochem Biophys Res Commun 272 (2000) 641-647
141. Dimitrova K.R., DeGroot K., Myers A.K., and Kim Y.D. Estrogen and homocysteine. Cardiovasc Res 53 (2002) 577-588
142. Roybal C.N., Yang S., Sun C.W., Hurtado D., Vander Jagt D.L., Townes T.M., et al. Homocysteine increases the expression of VEGF by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem 279 (2004) 14844-14852
143. Wang X.Z., Lawson B., Brewer J.W., Zinszner H., Sanjay A., Mi L.J., et al. Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein(CHOP/GADD153). Mol Cell Biol 16 (1996) 4273-4280
144. Cai Y., Zhang C., Nawa T., Aso T., Tanaka M., Oshiro S., et al. Homocysteine responsive ATF3 gene expression in human vascular endothelial cells: activation of c-Jun NH(2)-terminal kinase and promoter response element. Blood 96 (2000) 2140-2148
145. Zhang C., Kawauchi J., Adachi M.T., Hashimoto Y., Oshiro S., Aso T., et al. Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine. Biochem Biophys Res Commun 289 (2001) 718-724
146. Nishitani Y., and Matsumoto H. Ethanol rapidly causes activation of JNK associated with ER stress under inhibition of ADH. FEBS Lett 580 (2006) 9-14
147. Chen Y.R., Meyer C.F., and Tan T.H. Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation-induced apoptosis. J Biol Chem 271 (1996) 631-634
148. Watanabe M., Osada J., Aratani Y., Kluckman K., Reddick R., Malinow M.R., et al. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci USA 92 (1995) 1585-1589
149. Chen Z., Karaplis A.C., Ackerman S.L., Pogribny I.P., Melnyk S., Lussier-Cacan S., et al. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 10 (2001) 433-443
150. Ji C., Chan C., and Kaplowitz N. Predominant role of SREBP lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model. J Hepatol (2006) 10.1016/j.jhep.2006.05.009
151. Luigi E.A., Diego I., Giuseppe C., Amelia C., Maria D., et al. Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology 41 (2005) 995-1003