Interplay between hepatitis C virus and redox cell signaling

International Journal of Molecular Sciences

Volumn 14, Issue 3, 2013, Pages 4705-4721

  Ruggieri, Anna ^a   Anticoli, Simona ^b   Nencioni, Lucia ^b   Sgarbanti, Rossella ^c   Garaci, Enrico ^c   Palamara, Anna Teresa ^b,c  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c IRCCS SAN RAFFAELE PISANA   (Italy)

Author keywords

Akt; Antioxidants; GSH; HCV; JFH 1; MAPK; Oxidative stress

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE; NONSTRUCTURAL PROTEIN 5A; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 1; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; TRANSCRIPTION FACTOR NRF2; VIRUS PROTEIN;

ENZYME ACTIVITY; HEPATITIS C; HEPATITIS C VIRUS; HOST CELL; HUMAN; IN VITRO STUDY; LIFE CYCLE ASSESSMENT; LIFE CYCLE STAGE; MOLECULAR DYNAMICS; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; REDOX STRESS; REVIEW; SIGNAL TRANSDUCTION; VIRUS CELL INTERACTION; VIRUS REPLICATION;

EID: 84875077789     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms14034705     Document Type: Review

References (132)

1. Lavanchy, D. The global burden of hepatitis C. Liver Int. 2009, 29, 74-81.
2. Liang, T.J.; Heller, T. Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gastroenterology 2004, 127, S62-S71.
3. Moradpour, D.; Penin, F.; Rice, C.M. Replication of hepatitis C virus. Nat. Rev. Microbiol. 2007, 5, 453-463.
4. Herker, E.; Ott, M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol. Metab. 2011, 22, 241-248.
5. Manns, M.P.; Wedemeyer, H.; Cornberg, M. Treating viral hepatitis C: Efficacy, side effects, and complications. Gut 2006, 55, 1350-1359.
6. Hadziyannis, S.J.; Sette, H., Jr.; Morgan, T.R.; Balan, V.; Diago, M.; Marcellin, P.; Ramadori, G.; Bodenheimer, H., Jr.; Bernstein, D.; Rizzetto, M., et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann. Intern. Med. 2004, 140, 346-355.
7. Manns M.P.; McHutchison J.G.; Gordon S.C.; Rustgi, V.K.; Shiffman, M.; Reindollar, R.; Goodman, Z.D.; Koury, K.; Ling, M.; Albrecht, J.K. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet 2001, 358, 958-965.
8. Welsch, C.; Jesudian, A.; Zeuzem, S.; Jacobson, I. New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Gut 2012, 61, i36-i46.
9. Jacobson, I.M.; McHutchison, J.G.; Dusheiko, G.; Di Bisceglie, A.M.; Reddy, K.R.; Bzowej, N.H.; Marcellin, P.; Muir, A.J.; Ferenci, P.; Flisiak, R., et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N. Engl. J. Med. 2011, 364, 2405-2416.
10. Poordad, F.; McCone, J., Jr.; Bacon, B.R.; Bruno, S.; Manns, M.P.; Sulkowski, M.S.; Jacobson, I.M.; Reddy, K.R.; Goodman, Z.D.; Boparai, N., et al. Boceprevir for untreated chronic HCV genotype 1 infection. N. Engl. J. Med. 2011, 364, 1195-1206.
11. Sherman, K.E.; Flamm, S.L.; Afdhal, N.H.; Nelson, D.R.; Sulkowski, M.S.; Everson, G.T.; Fried, M.W.; Adler, M.; Reesink, H.W.; Martin, M., et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N. Engl. J. Med. 2011, 365, 1014-1024.
12. Sarrazin, C.; Hézode, C.; Zeuzem, S.; Pawlotsky, J.M. Antiviral strategies in hepatitis C virus infection. J. Hepatol. 2012, 56, S88-S100.
13. Bühler, S.; Bartenschlager, R. New targets for antiviral therapy of chronic hepatitis C. Liver Int. 2012, 32, 9-16.
14. Gallay, P.A. Cyclophilin inhibitors: A novel class of promising host-targeting anti-HCV agents. Immunol. Res. 2012, 52, 200-210.
15. Bode, J.G.; Brenndörfer, E.D.; Karthe, J.; Häussinger, D. Interplay between host cell and hepatitis C virus in regulating viral replication. Biol. Chem. 2009, 390, 1013-1032.
16. Menzel, N.; Fischl, W.; Hueging, K.; Bankwitz, D.; Frentzen, A.; Haid, S.; Gentzsch, J.; Kaderali, L.; Bartenschlager, R.; Pietschmann, T. MAP-kinase regulated cytosolic phospholipase A2 activity is essential for production of infectious hepatitis C virus particles. PLoS Pathog. 2012, 8, e1002829.
17. Mannová, P.; Beretta, L. Activation of the N-Ras-PI3K-Akt-mTOR pathway by hepatitis C virus: Control of cell survival and viral replication. J. Virol. 2005, 79, 8742-8749.
18. Liu, Z.; Tian, Y.; Machida, K.; Lai, M.M.; Luo, G.; Foung, S.K.; Ou, J.H. Transient activation of the PI3K-AKT pathway by HCV to enhance viral entry. J. Biol. Chem. 2012, 287, 41922-41930.
19. Cross, J.V.; Templeton, D.J. Regulation of signal transduction through protein cysteine oxidation. Antioxid. Redox Signal. 2006, 8, 1819-1827.
20. Filomeni, G.; Rotilio, G.; Ciriolo, M.R. Disulfide relays and phosphorylative cascades: Partners in redox-mediated signaling pathways. Cell Death Differ. 2005, 12, 1555-1563.
21. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.D.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell. Biol. 2007, 39, 44-84.
22. Meister, A.; Anderson, M.E. Glutathione. Ann. Rev. Biochem. 1983, 52, 711-760.
23. Forman, H.J.; Dickinson, D.A. Oxidative signaling and glutathione synthesis. Biofactors 2003, 17, 1-12.
24. Dalle-Donne, I.; Milzani, A.; Gagliano, N.; Colombo, R.; Giustarini, D.; Rossi, R. Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxid. Redox Signal. 2008, 10, 445-473.
25. Pastore, A.; Piemonte, F. S-Glutathionylation signaling in cell biology: Progress and prospects. Eur. J. Pharm. Sci. 2012, 46, 279-292.
26. Nencioni, L.; Sgarbanti, R.; Amatore, D.; Checconi, P.; Celestino, I.; Limongi, D.; Anticoli, S.; Palamara, A.T.; Garaci, E. Intracellular redox signaling as therapeutic target for novel antiviral strategy. Curr. Pharm. Des. 2011, 17, 3898-3904.
27. Fraternale, A.; Paoletti, M.F.; Casabianca, A.; Oiry, J.; Clayette, P.; Vogel, J.U.; Cynatl, J., Jr.; Palamara A.T.; Sgarbanti, R.; Garaci, E., et al. Antiviral and immunomodulatory properties of new pro-glutathione (GSH) molecules. Curr. Med. Chem. 2006, 13, 1749-1755.
28. Choi, J. Oxidative stress, endogenous antioxidants, alcohol, and hepatitis C: Pathogenic interactions and therapeutic considerations. Free Radic. Biol. Med. 2012, 52, 1135-1150.
29. Choi, J.; Ou, J.H. Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G847-G851.
30. Sgarbanti, R.; Nencioni, L.; Amatore, D.; Coluccio, P.; Fraternale, A.; Sale, P.; Mammola, C.L.; Carpino, G.; Gaudio, E.; Magnani, M., et al. Redox regulation of the influenza hemagglutinin maturation process: A new cell-mediated strategy for anti-influenza therapy. Antioxid. Redox Signal. 2011, 15, 593-606.
31. Kavouras, J.H.; Prandovszky, E.; Valyi-Nagy, K.; Kovacs, S.K.; Tiwari, V.; Kovacs, M.; Shukla, D.; Valyi-Nagy, T. Herpes simplex virus type 1 infection induces oxidative stress and the release of bioactive lipid peroxidation by-products in mouse P19N neural cell cultures. J. Neurovirol. 2007, 13, 416-425.
32. Peterhans, E. Oxidants and antioxidants in viral diseases: Disease mechanisms and metabolic regulation. J. Nutr. 1997, 127, S962-S965.
33. Seronello, S.; Sheikh, M.Y.; Choi, J. Redox regulation of hepatitis C in nonalcoholic and alcoholic liver. Free Radic. Biol. Med. 2007, 43, 869-882.
34. Mahmood, S.; Kawanaka, M.; Kamei, A.; Izumi, A.; Nakata, K.; Niiyama, G.; Ikeda, H.; Hanano, S.; Suehiro, M.; Togawa, K., et al. Immunohistochemical evaluation of oxidative stress markers in chronic hepatitis C. Antioxid. Redox Signal. 2004, 6, 19-24.
35. Romero, M.J.; Bosch-Morell, F.; Romero, B.; Rodrigo, J.M.; Serra, M.A.; Romero, F.J. Serum malondialdehyde: Possible use for the clinical management of chronic hepatitis C patients. Free Radic. Biol. Med. 1998, 25, 993-997.
36. Fujita, N.; Sugimoto, R.; Ma, N.; Tanaka, H.; Iwasa, M.; Kobayashi, Y.; Kawanishi, S.; Watanabe, S.; Kaito, M.; Takei, Y. Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J. Viral Hepat. 2008, 15, 498-507.
37. Farias, M.S.; Budni, P.; Ribeiro, C.M.; Parisotto, E.B.; Santos, C.E.; Dias, J.F.; Dalmarco, E.M.; Fröde, T.S.; Pedrosa, R.C.; Wilhelm Filho, D. Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients. Gastroenterol. Hepatol. 2012, 35, 386-394.
38. Lin, C.C.; Liu, W.H.; Wang, Z.H.; Yin, M.C. Vitamins B status and antioxidative defense in patients with chronic hepatitis B or hepatitis C virus infection. Eur. J. Nutr. 2011, 50, 499-506.
39. Barbaro, G.; Di Lorenzo, G.; Soldini, M.; Parrotto, S.; Bellomo, G.; Belloni, G.; Grisorio, B.; Barbarini, G. Hepatic glutathione deficiency in chronic hepatitis C: Quantitative evaluation in patients who are HIV positive and HIV negative and correlations with plasmatic and lymphocytic concentrations and with the activity of the liver disease. Am. J. Gastroenterol. 1996, 91, 2569-2573.
40. Loguercio, C.; Federico, A. Oxidative stress in viral and alcoholic hepatitis. Free Radic. Biol. Med. 2003, 34, 1-10.
41. Hosomura, N.; Kono, H.; Tsuchiya, M.; Ishii, K.; Ogiku, M.; Matsuda, M.; Fujii, H. HCV-related proteins activate Kupffer cells isolated from human liver tissues. Dig. Dis. Sci. 2011, 56, 1057-1064.
42. Thoren, F.; Romero, A.; Lindh, M.; Dahlgren, C.; Hellstrand, K. A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: Role of NADPH oxidase-derived oxygen radicals. J. Leukoc. Biol. 2004, 76, 1180-1186.
43. Vendemiale, G.; Grattagliano, I.; Portincasa, P.; Serviddio, G.; Palasciamo, G.; Altomare, E. Oxidative stress in symptom-free HCV carriers: Relation with ALT flare-up. Eur. J. Clin. Invest. 2001, 31, 54-63.
44. Moriya, K.; Nakagawa, K.; Santa, T.; Shintani, Y.; Fujie, H.; Miyoshi, H.; Tsutsumi, T.; Miyazawa, T.; Ishibashi, K.; Horie, T., et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res. 2001, 61, 4365-4370.
45. Korenaga, M.; Wang, T.; Li, Y.; Showalter, L.A.; Chan, T.; Sun, J.; Weinman, S.A. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J. Biol. Chem. 2005, 280, 37481-37488.
46. 2+ uniporter activity. FASEB J. 2007, 21, 2474-2485.
47. Machida, K.; Cheng, K.T.; Lai, C.K.; Jeng, K.S.; Sung, V.M.; Lai, M.M. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J. Virol. 2006, 80, 7199-7207.
48. Tardif, K.D.; Waris, G.; Siddiqui, A. Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol. 2005, 13, 159-163.
49. 2+ stores induced by hepatitis C NS5A protein. Biochem. Biophys. Res. Commun. 2008, 368, 593-599.
50. Tong, W.Y.; Nagano-Fujii, M.; Hidajat, R.; Deng, L.; Takigawa, Y.; Hotta, H. Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta. Biochem. Biophys. Res. Commun. 2002, 299, 366-372.
51. Chan, S.W.; Egan, P.A. Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response. FASEB J. 2005, 19, 1510-1512.
52. Santos, C.X.; Tanaka, L.Y.; Wosniak, J.; Laurindo, F.R. Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: Roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid. Redox. Signal. 2009, 11, 2409-2427.
53. De Mochel, N.S.R.; Seronello, S.; Wang, S.H. Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection. Hepatology 2010, 52, 47-59.
54. Boudreau, H.E.; Emerson, S.U.; Korzeniowska, A.; Jendrysik, M.A.; Leto, T.L. Hepatitis C virus (HCV) proteins induce NADPH oxidase 4 expression in a transforming growth factor beta-dependent manner: A new contributor to HCV-induced oxidative stress. J. Virol. 2009, 83, 12934-12946.
55. Diamond, D.L.; Syder, A.J.; Jacobs, J.M.; Sorensen, C.M.; Walters, K.A.; Proll, S.C.; McDermott, J.E.; Gritsenko, M.A.; Zhang, Q.; Zhao, R., et al. Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog. 2010, 6, e1000719.
56. Abdalla, M.Y.; Ahmad, I.M.; Spitz, D.R.; Schmidt, W.N.; Britigan, B.E. Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses. J. Med. Virol. 2005, 76, 489-497.
57. Qadri, I.; Iwahashi, M.; Capasso, J.M.; Hopken, M.W.; Flores, S.; Schaack, J.; Simon, F.R. Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: Role of JNK, p38 MAPK and AP-1. Biochem. J. 2004, 378, 919-928.
58. Li, K.; Prow, T.; Lemon, S.M.; Beard, M.R. Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells. Hepatology 2002, 35, 1237-1246.
59. Roe, B.; Kensicki, E.; Mohney, R.; Hall, W.W. Metabolomic profile of hepatitis C virus-infected hepatocytes. PLoS One 2011, 6, e23641.
60. Burdette, D.; Olivarez, M.; Waris, G. Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway. J. Gen. Virol. 2010, 91, 681-690.
61. Ivanov, A.V.; Smirnova, O.A.; Ivanova, O.N.; Masalova, O.V.; Kochetkov, S.N.; Isaguliants, M.G. Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells. PLoS One 2011, 6, e24957.
62. Carvajal-Yepes, M.; Himmelsbach, K.; Schaedler, S.; Ploen, D.; Krause, J.; Ludwig, L.; Weiss, T.; Klingel, K.; Hildt, E. Hepatitis C virus impairs the induction of cytoprotective Nrf2 target genes by delocalization of small Maf proteins. J. Biol. Chem. 2011, 286, 8941-8951.
63. Motohashi, H.; Yamamoto, M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol. Med. 2004, 10, 549-557.
64. Rushmore, T.H.; Morton, M.R.; Pickett, C.B. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem. 1991, 266, 11632-11639.
65. Garaci, E.; Palamara, A.T.; Ciriolo, M.R.; D'Agostini, C.; Abdel-Latif, M.S.; Aquaro, S.; Lafavia, E.; Rotilio, G. Intracellular GSH content and HIV replication in human macrophages. J. Leukoc. Biol. 1997, 62, 54-59.
66. Clement, S.; Pascarella, S.; Negro, F. Hepatitis C Virus infection: Molecular pathways to steatosis, insulin resistance and oxidative stress. Viruses 2009, 1, 126-143.
67. Tanikawa, K.; Torimura, T. Studies on oxidative stress in liver diseases: Important future trends in liver research. Med. Mol. Morphol. 2006, 39, 22-27.
68. Melhem, A.; Stern, M.; Shibolet, O.; Israeli, E.; Ackerman, Z.; Pappo, O.; Hemed, N.; Rowe, M.; Ohana, H.; Zabrecky, G., et al. Treatment of chronic hepatitis C virus infection via antioxidants: Results of a phase I clinical trial. J. Clin. Gastroenterol. 2005, 39, 737-742.
69. Choi, J.; Lee, K.J.; Zheng, Y.; Yamaga, A.K.; Lai M.M.; Ou, J.H. Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells. Hepatology 2004, 39, 81-89.
70. Choi, J.; Forman, H.J.; Ou, J.H.; Lai, M.M.; Seronello, S.; Nandipati, A. Redox modulation of the hepatitis C virus replication complex is calcium dependent. Free Radic. Biol. Med. 2006, 41, 1488-1498.
71. Seronello, S.; Ito, C.; Wakita, T.; Choi, J. Ethanol enhances hepatitis C virus replication through lipid metabolism and elevated NADH/NAD+. J. Biol. Chem. 2010, 285, 845-854.
72. Kuroki, M.; Ariumi, Y.; Ikeda, M.; Dansako, H.; Wakita, T.; Kato N. Arsenic trioxide inhibits hepatitis C virus RNA replication through modulation of the glutathione redox system and oxidative stress. J. Virol. 2009, 83, 2338-2348.
73. Yano, M.; Ikeda, M.; Abe, K.; Dansako, H.; Ohkoshi, S.; Aoyagi, Y.; Kato, N. Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture. Antimicrob. Agents Chemother. 2007, 51, 2016-2027.
74. Nakamura, M.; Saito, H.; Ikeda, M.; Hokari, R.; Kato, N.; Hibi, T.; Miura, S. An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. World J. Gastroenterol. 2010, 16, 184-192.
75. McCartney, E.M.; Beard, M.R. Impact of alcohol on hepatitis C virus replication and interferon signaling. World J. Gastroenterol. 2010, 16, 1337-1343.
76. Waris, G.; Turkson, J.; Hassanein, T.; Siddiqui, A. Hepatitis C virus (HCV) constitutively activates STAT-3 via oxidative stress: Role of STAT-3 in HCV replication. J. Virol. 2005, 79, 1569-1580.
77. Rivas-Estilla, A.M.; Bryan-Marrugo, O.L.; Trujillo-Murillo, K.; Pérez-Ibave, D.; Charles-Niño, C.; Pedroza-Roldan, C.; Ríos-Ibarra, C.; Ramírez-Valles, E.; Ortiz-López, R.; Islas-Carbajal, M.C., et al. Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302, G1264-G1273.
78. Wagoner, J.; Negash, A.; Kane, O.J., Martinez L.E.; Nahmias, Y.; Bourne, N.; Owen, D.M.; Grove, J.; Brimacombe, C.; McKeating, J.A., et al. Multiple effects of silymarin on the hepatitis C virus life cycle. Hepatology 2010, 51, 1912-1921.
79. Wagoner, J.; Morishima, C.; Graf, T.N.; Oberlies, N.H.; Teissier, E.; Pécheur, E.I.; Tavis, J.E.; Polyak, S.J. Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation. PLoS One 2011, 6, e16464.
80. Goldwasser, J.; Cohen, P.Y.; Lin, W.; Kitsberg, D.; Balaguer, P.; Polyak, S.J.; Chung, R.T.; Yarmush, M.L.; Nahmias, Y. Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism. J. Hepatol. 2011, 55, 963-971.
81. Nahmias, Y.; Goldwasser, J.; Casali, M.; van Poll, D.; Wakita, T.; Chung, R.T.; Yarmush, M.L. Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatology 2008, 47, 1437-1445.
82. Khachatoorian, R.; Arumugaswami, V.; Raychaudhuri, S.; Yeh, G.K.; Maloney, E.M.; Wang, J.; Dasgupta, A.; French, S.W. Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle. Virology 2012, 433, 346-355.
83. Bachmetov, L.; Gal-Tanamy, M.; Shapira, A.; Vorobeychik, M.; Giterman-Galam, T.; Sathiyamoorthy, P.; Golan-Goldhirsh, A.; Benhar, I.; Tur-Kaspa, R.; Zemel, R. Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity. J. Viral. Hepat. 2012, 19, e81-e88.
84. Kim, K.; Kim, K.H.; Kim, H.Y.; Cho, H.K.; Sakamoto, N.; Cheong, J. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. FEBS Lett. 2010, 584, 707-712.
85. Guedj, J.; Dahari, H.; Pohl, R.T.; Ferenci, P.; Perelson, A.S. Understanding silibinin's modes of action against HCV using viral kinetic modeling. J. Hepatol. 2012, 56, 1019-1024.
86. Falasca, K.; Ucciferri, C.; Mancino, P.; Vitacolonna, E.; De Tullio, D.; Pizzigallo, E.; Conti, P.; Vecchiet, J. Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection. J. Med. Virol. 2008, 80, 1900-1906.
87. Powis, G. Free radical formation by antitumor quinones. Free Radic. Biol. Med. 1989, 6, 63-101.
88. Monks, T.J.; Hanzlik, R.P.; Cohen, G.M.; Ross, D.; Graham, D.G. Quinone chemistry and toxicity. Toxicol. Appl. Pharmacol. 1992, 112, 2-16.
89. Wang, A.L.; Wang, J.P.; Wang, H.; Chen, Y.H.; Zhao, L.; Wang, L.S.; Wei, W.; Xu, D.X. A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice. Hepatol. Res. 2006, 34, 199-206.
90. Palamara, A.T.; Nencioni, L.; Aquilano, K; De Chiara, G.; Hernandez, L.; Cozzolino, F.; Ciriolo, M.R.; Garaci, E. Inhibition of influenza A virus replication by resveratrol. J. Infect. Dis. 2005, 191, 1719-1729.
91. Burkitt, M.J.; Duncan, J. Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: Evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. Archiv. Biochem. Biophys. 2000, 381, 253-263.
92. Chang, Y.C.; Chuang, L.M. The role of oxidative stress in the pathogenesis of type 2 diabetes: From molecular mechanism to clinical implication. Am. J. Transl. Res. 2010, 2, 316-331.
93. Torres, M.; Forman, H.J. Redox signaling and the MAP kinase pathways. Biofactors 2003, 17, 287-296.
94. McCubrey, J.A.; Lahair, M.M.; Franklin, R.A. Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid. Redox. Signal. 2006, 8, 1775-1789.
95. Leslie, N.R. The redox regulation of PI 3-kinase-dependent signaling. Antioxid. Redox. Signal. 2006, 8, 1765-1774.
96. Nencioni, L.; de Chiara, G.; Sgarbanti, R.; Amatore, D.; Aquilano, K.; Marcocci, M.E.; Serafino, A.; Torcia, M.; Cozzolino, F., Ciriolo, M.R., et al. Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: Impact on virally induced apoptosis and viral replication. J. Biol. Chem. 2009, 284, 16004-16015.
97. Nencioni, L.; Sgarbanti, R.; De Chiara, G.; Garaci, E.; Palamara, A.T. Influenza virus and redox mediated cell signaling: A complex network of virus/host interaction. New Microbiol. 2007, 30, 367-375.
98. Shin, Y.K.; Liu, Q.; Tikoo, S.K.; Babiuk, L.A.; Zhou, Y. Effect of the phosphatidylinositol 3-kinase/Akt pathway on influenza A virus propagation. J. Gen. Virol. 2007, 88, 942-950.
99. Muthumani, K.; Wadsworth, S.A.; Dayes, N.S.; Hwang, D.S.; Choo, A.Y.; Abeysinghe, H.R.; Siekierka, J.J.; Weiner, D.B. Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38/JNK kinase inhibitor. AIDS 2004, 18, 739-748.
100. Yu, Y.; Alwine, J.C. Human cytomegalovirus major immediate-early proteins and simian virus 40 large T antigen can inhibit apoptosis through activation of the phosphatidylinositide 3'-OH kinase pathway and the cellular kinase Akt. J. Virol. 2002, 76, 3731-3738.
101. Rahaus, M.; Desloges, N.; Wolff, M.H. Varicella-zoster virus requires a functional PI3K/Akt/GSK-3alpha/beta signaling cascade for efficient replication. Cell Signal. 2007, 19, 312-320.
102. Lahair, M.M.; Howe, C.J.; Rodriguez-Mora, O.; McCubrey, J.A.; Franklin, R.A. Molecular pathways leading to oxidative stress-induced phosphorylation of Akt. Antioxid. Redox Signal. 2006, 8, 1749-1756.
103. Waris G, Siddiqui A. Hepatitis C virus stimulates the expression of cyclooxygenase-2 via oxidative stress: Role of prostaglandin E2 in RNA replication. J. Virol. 2005, 79, 9725-9734.
104. 2-induced activation of ERK1/2, p38 MAPK, and protein kinase B signaling in vascular smooth muscle cells. Antioxid. Redox Signal. 2004, 6, 353-366.
105. 2-stressed human cardiac microvascular endothelium. Am. J. Physiol. Heart Circ. Physiol. 2008, 295, H2417-H2426.
106. 2-induced phosphorylation of ERK1/2 and PKB requires tyrosine kinase activity of insulin receptor and c-Src. Antioxid. Redox Signal. 2005, 7, 1014-1020.
107. Conde de la Rosa, L.; Schoemaker, M.H.; Vrenken, T.E.; Buist-Homan, M.; Havinga, R.; Jansen, P.L.; Moshage, H. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: Involvement of JNK and ERK MAP kinases. J. Hepatol. 2006, 44, 918-929.
108. Aikawa, R.; Komuro, I.; Yamazaki, T.; Zou, Y.; Kudoh, S.; Tanaka, M.; Shiojima, I.; Hiroi, Y.; Yazaki, Y. Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J. Clin. Invest. 1997, 100, 1813-1821.
109. Lee, S.R.; Kwon, K.S.; Kim, S.R.; Rhee, S.G. Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J. Biol. Chem. 1998, 273, 15366-15372.
110. Liu, H.; Nishitoh, H.; Ichijo, H.; Kyriakis, J.M. Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin. Mol. Cell Biol. 2000, 20, 2198-2208.
111. Saitoh, M.; Nishitoh, H.; Fujii, M.; Takeda, K.; Tobiume, K.; Sawada, Y.; Kawabata, M.; Miyazono, K.; Ichijo, H. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 1998, 17, 2596-2606.
112. Matsukawa, J.; Matsuzawa, A.; Takeda, K.; Ichijo, H. The ASK1-MAP kinase cascades in mammalian stress response. J. Biochem. 2004, 136, 261-265.
113. Adler, V.; Yin, Z.; Fuchs, S.Y.; Benezra, M.; Rosario, L.; Tew, K.D.; Pincus, M.R.; Sardana, M.; Henderson, C.J.; Wolf, C.R., et al. Regulation of JNK signaling by GSTp. EMBO J. 1999, 18, 1321-1334.
114. 2. J. Biol. Chem. 2002, 277, 20336-20342.
115. Leslie, N.R.; Bennett, D.; Lindsay, Y.E.; Stewart, H.; Gray, A.; Downes, C.P. Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J. 2003, 22, 5501-5510.
116. Mazzocca, A.; Sciammetta, S.C.; Carloni, V.; Cosmi, L.; Annunziato, F.; Harada, T.; Abrignani, S.; Pinzani, M. Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J. Biol. Chem. 2005, 280, 11329-11339.
117. Ming-Ju, H.; Yih-Shou, H.; Tzy-Yen, C.; Hui-Ling, C. Hepatitis C virus E2 protein induce reactive oxygen species (ROS)-related fibrogenesis in the HSC-T6 hepatic stellate cell line. J. Cell Biochem. 2011, 112, 233-243.
118. Lin, W.; Tsai, W.L.; Shao, R.X.; Wu, G.; Peng, L.F.; Barlow, L.L.; Chung, W.J.; Zhang, L.; Zhao, H.; Jang, J.Y., et al. Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner. Gastroenterology. 2010, 138, 2509-2518.
119. Street, A.; Macdonald, A.; McCormick, C.; Harris, M. Hepatitis C virus NS5A-mediated activation of phosphoinositide 3-kinase results in stabilization of cellular beta-catenin and stimulation of beta-catenin-responsive transcription. J. Virol. 2005, 79, 5006-5016.
120. Street, A.; Macdonald, A.; Crowder, K.; Harris, M. The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade. J. Biol. Chem. 2004, 279, 12232-12241.
121. Frelin, L.; Brenndörfer, E.D.; Ahlén, G.; Weiland, M.; Hultgren, C.; Alheim, M.; Glaumann, H.; Rozell, B.; Milich, D.R.; Bode, J.G., et al. The hepatitis C virus and immune evasion: Non-structural 3/4A transgenic mice are resistant to lethal tumour necrosis factor alpha mediated liver disease. Gut 2006, 55, 1475-1483.
122. Brazzoli, M.; Bianchi, A.; Filippini, S.; Weiner, A.; Zhu, Q.; Pizza, M.; Crotta, S. CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. J. Virol. 2008, 82, 8316-8329.
123. Pei, R.; Chen, H.; Lu, L.; Zhu, W.; Beckebaum, S.; Cicinnati, V.; Lu, M.; Chen, X. Hepatitis C virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly. J. Gen. Virol. 2011, 92, 2237-2248.
124. Murata, T.; Hijikata, M.; Shimotohno, K. Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059. Virology 2005, 340, 105-115.
125. Huang, Y.; Chen, X.C.; Konduri, M.; Fomina, N.; Lu, J.; Jin, L.; Kolykhalov, A.; Tan, S.L. Mechanistic link between the anti-HCV effect of interferon gamma and control of viral replication by a Ras-MAPK signaling cascade. Hepatology 2006, 43, 81-90.
126. Yano, M.; Ikeda, M.; Abe, K.; Kawai, Y.; Kuroki, M.; Mori, K.; Dansako, H.; Ariumi, Y.; Ohkoshi, S.; Aoyagi, Y., et al. Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase. Hepatology 2009, 50, 678-688.
127. Brenndörfer, E.D.; Karthe, J.; Frelin, L.; Cebula, P.; Erhardt, A.; Schulte am Esch, J.; Hengel, H.; Bartenschlager, R.; Sällberg, M.; Häussinger, D., et al. Nonstructural 3/4A protease of hepatitis C virus activates epithelial growth factor-induced signal transduction by cleavage of the T-cell protein tyrosine phosphatase. Hepatology 2009, 49, 1810-1820.
128. Mankouri, J.; Tedbury, P.R.; Gretton, S.; Hughes, M.E.; Griffin, S.D.; Dallas, M.L.; Green, K.A.; Hardie, D.G., Peers, C.; Harris, M. Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase. Proc. Natl. Acad. Sci. USA 2010, 107, 11549-11554.
129. Fukuhara, T.; Matsuura, Y. Role of miR-122 and lipid metabolism in HCV infection. J. Gastroenterol. 2012, 48, 169-176.
130. Syed, G.H.; Amako, Y.; Siddiqui, A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol. Metab. 2010, 21, 33-40.
131. Aizaki, H.; Lee, K.J.; Sung, V.M.; Ishiko, H.; Lai, M.M. Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts. Virology 2004, 324, 450-461.
132. Miyanari, Y.; Atsuzawa, K.; Usuda, N.; Watashi, K.; Hishiki, T.; Zayas, M.; Bartenschlager, R.; Wakita, T.; Hijikata, M.; Shimotohno, K. The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell. Biol. 2007, 9, 1089-1097.