Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 8327410, 15 pages
http://dx.doi.org/10.1155/2016/8327410
Review Article

Oxidative Stress in the Healthy and Wounded Hepatocyte: A Cellular Organelles Perspective

1Department of Biomedical Clinical and Experimental Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
2Careggi University Hospital, 50134 Florence, Italy

Received 25 July 2015; Accepted 10 September 2015

Academic Editor: Pablo Muriel

Copyright © 2016 Tommaso Mello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. P. Jones, “Radical-free biology of oxidative stress,” The American Journal of Physiolog—Cell Physiology, vol. 295, no. 4, pp. C849–C868, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. P. D. Ray, B.-W. Huang, and Y. Tsuji, “Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling,” Cellular Signalling, vol. 24, no. 5, pp. 981–990, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. D. P. Jones and Y.-M. Go, “Redox compartmentalization and cellular stress,” Diabetes, Obesity and Metabolism, vol. 12, supplement 2, pp. 116–125, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. C. C. Winterbourn, “Are free radicals involved in thiol-based redox signaling?” Free Radical Biology and Medicine, vol. 80, pp. 164–170, 2015. View at Publisher · View at Google Scholar
  5. H. Sies, “Oxidative stress: a concept in redox biology and medicine,” Redox Biology, vol. 4, pp. 180–183, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. L. L. Ji, M.-C. Gomez-Cabrera, and J. Vina, “Exercise and hormesis: activation of cellular antioxidant signaling pathway,” Annals of the New York Academy of Sciences, vol. 1067, no. 1, pp. 425–435, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Schieber and N. S. Chandel, “ROS function in redox signaling and oxidative stress,” Current Biology, vol. 24, no. 10, pp. R453–R462, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. G. Bjelakovic, D. Nikolova, L. L. Gluud, R. G. Simonetti, and C. Gluud, “Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis,” Journal of the American Medical Association, vol. 297, no. 8, pp. 842–857, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. R.-M. Liu, J. Choi, J.-H. Wu et al., “Oxidative modification of nuclear mitogen-activated protein kinase phosphatase 1 is involved in transforming growth factor β1-induced expression of plasminogen activator inhibitor 1 in fibroblasts,” The Journal of Biological Chemistry, vol. 285, no. 21, pp. 16239–16247, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Benčina, “Illumination of the spatial order of intracellular pH by genetically encoded pH-sensitive sensors,” Sensors, vol. 13, no. 12, pp. 16736–16758, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. K. A. Lukyanov and V. V. Belousov, “Genetically encoded fluorescent redox sensors,” Biochimica et Biophysica Acta, vol. 1840, no. 2, pp. 745–756, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. S. G. Rhee, T.-S. Chang, W. Jeong, and D. Kang, “Methods for detection and measurement of hydrogen peroxide inside and outside of cells,” Molecules and Cells, vol. 29, no. 6, pp. 539–549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. V. Zámbó, L. Simon-Szabó, P. Szelényi, É. Kereszturi, G. Bánhegyi, and M. Csala, “Lipotoxicity in the liver,” World Journal of Hepatology, vol. 5, no. 10, pp. 550–557, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. E. Ceni, T. Mello, and A. Galli, “Pathogenesis of alcoholic liver disease: role of oxidative metabolism,” World Journal of Gastroenterology, vol. 20, no. 47, pp. 17756–17772, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Mello, E. Ceni, C. Surrenti, and A. Galli, “Alcohol induced hepatic fibrosis: role of acetaldehyde,” Molecular Aspects of Medicine, vol. 29, no. 1-2, pp. 17–21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Dongiovanni, A. L. Fracanzani, S. Fargion, and L. Valenti, “Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target,” Journal of Hepatology, vol. 55, no. 4, pp. 920–932, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Fujita and Y. Takei, “Iron overload in nonalcoholic steatohepatitis,” Advances in Clinical Chemistry, vol. 55, pp. 105–132, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. J. E. Nelson, H. Klintworth, and K. V. Kowdley, “Iron metabolism in Nonalcoholic Fatty Liver Disease,” Current Gastroenterology Reports, vol. 14, no. 1, pp. 8–16, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Arciello, M. Gori, and C. Balsano, “Mitochondrial dysfunctions and altered metals homeostasis: new weapons to counteract HCV-related oxidative stress,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 971024, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Hino, S. Nishina, and Y. Hara, “Iron metabolic disorder in chronic hepatitis C: mechanisms and relevance to hepatocarcinogenesis,” Journal of Gastroenterology and Hepatology, vol. 28, no. 4, pp. 93–98, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. D. P. Jones and H. Sies, “The redox code,” Antioxidants & Redox Signaling, 2015. View at Publisher · View at Google Scholar
  22. P. Venkatakrishnan, E. S. Nakayasu, I. C. Almeida, and R. T. Miller, “Absence of nitric-oxide synthase in sequentially purified rat liver mitochondria,” Journal of Biological Chemistry, vol. 284, no. 30, pp. 19843–19855, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. J. S. Stamler, D. J. Singel, and C. A. Piantadosi, “SNO-hemoglobin and hypoxic vasodilation,” Nature Medicine, vol. 14, no. 10, pp. 1008–1009, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. A.-L. Levonen, R. P. Patel, P. Brookes et al., “Mechanisms of cell signaling by nitric oxide and peroxynitrite: from mitochondria to MAP kinases,” Antioxidants and Redox Signaling, vol. 3, no. 2, pp. 215–229, 2001. View at Publisher · View at Google Scholar · View at Scopus
  25. P. Pacher, J. S. Beckman, and L. Liaudet, “Nitric oxide and peroxynitrite in health and disease,” Physiological Reviews, vol. 87, no. 1, pp. 315–424, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Denicola, J. M. Souza, and R. Radi, “Diffusion of peroxynitrite across erythrocyte membranes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 7, pp. 3566–3571, 1998. View at Publisher · View at Google Scholar · View at Scopus
  27. D. B. Zorov, C. R. Filburn, L.-O. Klotz, J. L. Zweier, and S. J. Sollott, “Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes,” Journal of Experimental Medicine, vol. 192, no. 7, pp. 1001–1014, 2000. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Tandara and I. Salamunic, “Iron metabolism: current facts and future directions,” Biochemia Medica, vol. 22, no. 3, pp. 311–328, 2012. View at Google Scholar · View at Scopus
  29. N. Bresgen and P. M. Eckl, “Oxidative stress and the homeodynamics of iron metabolism,” Biomolecules, vol. 5, no. 2, pp. 808–847, 2015. View at Publisher · View at Google Scholar
  30. R. Lill, B. Hoffmann, S. Molik et al., “The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1823, no. 9, pp. 1491–1508, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. E. B. Tahara, F. D. T. Navarete, and A. J. Kowaltowski, “Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation,” Free Radical Biology and Medicine, vol. 46, no. 9, pp. 1283–1297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. J. St-Pierre, J. A. Buckingham, S. J. Roebuck, and M. D. Brand, “Topology of superoxide production from different sites in the mitochondrial electron transport chain,” The Journal of Biological Chemistry, vol. 277, no. 47, pp. 44784–44790, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Kaludercic, A. Carpi, T. Nagayama et al., “Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts,” Antioxidants and Redox Signaling, vol. 20, no. 2, pp. 267–280, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Staniek and H. Nohl, “Are mitochondria a permanent source of reactive oxygen species?” Biochimica et Biophysica Acta—Bioenergetics, vol. 1460, no. 2-3, pp. 268–275, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. G. C. Brown and V. Borutaite, “There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells,” Mitochondrion, vol. 12, no. 1, pp. 1–4, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Boveris, N. Oshino, and B. Chance, “The cellular production of hydrogen peroxide,” Biochemical Journal, vol. 128, no. 3, pp. 617–630, 1972. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Bakala, M. Hamelin, J. Mary, C. Borot-Laloi, and B. Friguet, “Catalase, a target of glycation damage in rat liver mitochondria with aging,” The Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1822, no. 10, pp. 1527–1534, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. O. W. Griffith and A. Meister, “Origin and turnover of mitochondrial glutathione,” Proceedings of the National Academy of Sciences of the United States of America, vol. 82, no. 14, pp. 4668–4672, 1985. View at Publisher · View at Google Scholar · View at Scopus
  39. K. Kurosawa, N. Hayashi, N. Sato, T. Kamada, and K. Tagawa, “Transport of glutathione across the mitochondrial membranes,” Biochemical and Biophysical Research Communications, vol. 167, no. 1, pp. 367–372, 1990. View at Publisher · View at Google Scholar · View at Scopus
  40. Z. Chen and L. H. Lash, “Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers,” The Journal of Pharmacology and Experimental Therapeutics, vol. 285, no. 2, pp. 608–618, 1998. View at Google Scholar · View at Scopus
  41. Z. Chen, D. A. Putt, and L. H. Lash, “Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria. Further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport,” Archives of Biochemistry and Biophysics, vol. 373, no. 1, pp. 193–202, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. O. Coll, A. Colell, C. García-Ruiz, N. Kaplowitz, and J. C. Fernández-Checa, “Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion,” Hepatology, vol. 38, no. 3, pp. 692–702, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. H. M. Wilkins, K. Marquardt, L. H. Lash, and D. A. Linseman, “Bcl-2 is a novel interacting partner for the 2-oxoglutarate carrier and a key regulator of mitochondrial glutathione,” Free Radical Biology and Medicine, vol. 52, no. 2, pp. 410–419, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Legault, C. Carrier, P. Petrov, P. Renard, J. Remacle, and M.-E. Mirault, “Mitochondrial GPx1 decreases induced but not basal oxidative damage to mtDNA in T47D cells,” Biochemical and Biophysical Research Communications, vol. 272, no. 2, pp. 416–422, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Marí, A. Morales, A. Colell, C. García-Ruiz, and J. C. Fernández-Checa, “Mitochondrial glutathione, a key survival antioxidant,” Antioxidants and Redox Signaling, vol. 11, no. 11, pp. 2685–2700, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. B. Chance, H. Sies, and A. Boveris, “Hydroperoxide metabolism in mammalian organs,” Physiological Reviews, vol. 59, no. 3, pp. 527–605, 1979. View at Google Scholar · View at Scopus
  47. P. Cole-Ezea, D. Swan, D. Shanley, and J. Hesketh, “Glutathione peroxidase 4 has a major role in protecting mitochondria from oxidative damage and maintaining oxidative phosphorylation complexes in gut epithelial cells,” Free Radical Biology and Medicine, vol. 53, no. 3, pp. 488–497, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. P. H. Willems, R. Rossignol, C. E. Dieteren, M. P. Murphy, and W. J. Koopman, “Redox homeostasis and mitochondrial dynamics,” Cell Metabolism, vol. 22, no. 2, pp. 207–218, 2015. View at Publisher · View at Google Scholar
  49. J. C. Fernández-Checa, C. García-Ruiz, M. Ookhtens, and N. Kaplowitz, “Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed rats tracer kinetic studies in vitro and in vivo and susceptibility to oxidant stress,” The Journal of Clinical Investigation, vol. 87, no. 2, pp. 397–405, 1991. View at Publisher · View at Google Scholar · View at Scopus
  50. J. C. Fernandez-Checa, M. Ookhtens, and N. Kaplowitz, “Effects of chronic ethanol feeding on rat hepatocytic glutathione. Relationship of cytosolic glutathione to efflux and mitochondrial sequestration,” The Journal of Clinical Investigation, vol. 83, no. 4, pp. 1247–1252, 1989. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Hirano, N. Kaplowitz, H. Tsukamoto, S. Kamimura, and J. C. Fernandez-Checa, “Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats,” Hepatology, vol. 16, no. 6, pp. 1423–1427, 1992. View at Publisher · View at Google Scholar · View at Scopus
  52. Y.-M. Go and D. P. Jones, “Redox compartmentalization in eukaryotic cells,” Biochimica et Biophysica Acta, vol. 1780, no. 11, pp. 1273–1290, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Ricci, V. Pastukh, J. Leonard et al., “Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis,” American Journal of Physiology—Cell Physiology, vol. 294, no. 2, pp. C413–C422, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Mansouri, I. Gaou, C. De Kerguenec et al., “An alcoholic binge causes massive degradation of hepatic mitochondrial DNA in mice,” Gastroenterology, vol. 117, no. 1, pp. 181–190, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. C. Demeilliers, C. Maisonneuve, A. Grodet et al., “Impaired adaptive resynthesis and prolonged depletion of hepatic mitochondrial DNA after repeated alcohol binges in mice,” Gastroenterology, vol. 123, no. 4, pp. 1278–1290, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. F. Chiappini, A. Barrier, R. Saffroy et al., “Exploration of global gene expression in human liver steatosis by high-density oligonucleotide microarray,” Laboratory Investigation, vol. 86, no. 2, pp. 154–165, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Kawahara, M. Fukura, M. Tsuchishima, and S. Takase, “Mutation of mitochondrial DNA in livers from patients with alcoholic hepatitis and nonalcoholic steatohepatitis,” Alcoholism: Clinical and Experimental Research, vol. 31, no. 1, pp. S54–S60, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. C. S. Lieber, “Ethanol metabolism, cirrhosis and alcoholism,” Clinica Chimica Acta, vol. 257, no. 1, pp. 59–84, 1997. View at Publisher · View at Google Scholar · View at Scopus
  59. C. S. Lieber, “Metabolic effects of acetaldehyde,” Biochemical Society Transactions, vol. 16, no. 3, pp. 241–247, 1988. View at Publisher · View at Google Scholar · View at Scopus
  60. J. A. Doorn, T. D. Hurley, and D. R. Petersen, “Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal and 4-oxonon-2-enal,” Chemical Research in Toxicology, vol. 19, no. 1, pp. 102–110, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Jin, J. Chen, L. Chen et al., “ALDH2 (E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis,” Proceedings of the National Academy of Sciences, vol. 112, no. 29, pp. 9088–9093, 2015. View at Publisher · View at Google Scholar
  62. S. H. Caldwell, R. H. Swerdlow, E. M. Khan et al., “Mitochondrial abnormalities in non-alcoholic steatohepatitis,” Journal of Hepatology, vol. 31, no. 3, pp. 430–434, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Seki, T. Kitada, T. Yamada, H. Sakaguchi, K. Nakatani, and K. Wakasa, “In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases,” Journal of Hepatology, vol. 37, no. 1, pp. 56–62, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Pérez-Carreras, P. Del Hoyo, M. A. Martín et al., “Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis,” Hepatology, vol. 38, no. 4, pp. 999–1007, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. L. Llacuna, A. Fernández, C. V. Montfort et al., “Targeting cholesterol at different levels in the mevalonate pathway protects fatty liver against ischemia-reperfusion injury,” Journal of Hepatology, vol. 54, no. 5, pp. 1002–1010, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. L. A. Videla, R. Rodrigo, M. Orellana et al., “Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients,” Clinical Science, vol. 106, no. 3, pp. 261–268, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Gambino, G. Musso, and M. Cassader, “Redox balance in the pathogenesis of nonalcoholic fatty liver disease: mechanisms and therapeutic opportunities,” Antioxidants and Redox Signaling, vol. 15, no. 5, pp. 1325–1365, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. C. von Montfort, N. Matias, A. Fernandez et al., “Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis,” Journal of Hepatology, vol. 57, no. 4, pp. 852–859, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Borgese, M. Francolini, and E. Snapp, “Endoplasmic reticulum architecture: structures in flux,” Current Opinion in Cell Biology, vol. 18, no. 4, pp. 358–364, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Chakravarthi and N. J. Bulleid, “Glutathione is required to regulate the formation of native disulfide bonds within proteins entering the secretory pathway,” Journal of Biological Chemistry, vol. 279, no. 38, pp. 39872–39879, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Higa and E. Chevet, “Redox signaling loops in the unfolded protein response,” Cellular Signalling, vol. 24, no. 8, pp. 1548–1555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. J. D. Malhotra and R. J. Kaufman, “Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword?” Antioxidants and Redox Signaling, vol. 9, no. 12, pp. 2277–2293, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Csala, É. Margittai, and G. Bánhegyi, “Redox control of endoplasmic reticulum function,” Antioxidants & Redox Signaling, vol. 13, no. 1, pp. 77–108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. J. W. Cuozzo and C. A. Kaiser, “Competition between glutathione and protein thiols for disulphide-bond formation,” Nature Cell Biology, vol. 1, no. 3, pp. 130–135, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. K. Zhang and R. J. Kaufman, “From endoplasmic-reticulum stress to the inflammatory response,” Nature, vol. 454, no. 7203, pp. 455–462, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. X. Shen, K. Zhang, and R. J. Kaufman, “The unfolded protein response—a stress signaling pathway of the endoplasmic reticulum,” Journal of Chemical Neuroanatomy, vol. 28, no. 1-2, pp. 79–92, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. P. I. Merksamer and F. R. Papa, “The UPR and cell fate at a glance,” Journal of Cell Science, vol. 123, no. 7, pp. 1003–1006, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. E. Passos, A. Ascensão, M. J. Martins, and J. Magalhães, “Endoplasmic reticulum stress response in non-alcoholic steatohepatitis: the possible role of physical exercise,” Metabolism, vol. 64, no. 7, pp. 780–792, 2015. View at Publisher · View at Google Scholar
  79. D. Acosta-Alvear, Y. Zhou, A. Blais et al., “XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks,” Molecular Cell, vol. 27, no. 1, pp. 53–66, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. K. Zhang, S. Wang, J. Malhotra et al., “The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis,” The EMBO Journal, vol. 30, no. 7, pp. 1357–1375, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Ron and S. R. Hubbard, “How IRE1 reacts to ER stress,” Cell, vol. 132, no. 1, pp. 24–26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. H. P. Harding, Y. Zhang, H. Zeng et al., “An integrated stress response regulates amino acid metabolism and resistance to oxidative stress,” Molecular Cell, vol. 11, no. 3, pp. 619–633, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. S. B. Cullinan, D. Zhang, M. Hannink, E. Arvisais, R. J. Kaufman, and J. A. Diehl, “Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival,” Molecular and Cellular Biology, vol. 23, no. 20, pp. 7198–7209, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Mathers, J. A. Fraser, M. McMahon, R. D. C. Saunders, J. D. Hayes, and L. I. McLellan, “Antioxidant and cytoprotective responses to redox stress,” Biochemical Society Symposium, vol. 71, pp. 157–176, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. D. D. Zhang, “Mechanistic studies of the Nrf2-Keap1 signaling pathway,” Drug Metabolism Reviews, vol. 38, no. 4, pp. 769–789, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. S. B. Cullinan and J. A. Diehl, “PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress,” The Journal of Biological Chemistry, vol. 279, no. 19, pp. 20108–20117, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. J. B. DuRose, D. Scheuner, R. J. Kaufman, L. I. Rothblum, and M. Niwa, “Phosphorylation of eukaryotic translation initiation factor 2α coordinates rRNA transcription and translation inhibition during endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 29, no. 15, pp. 4295–4307, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. X. Chen, J. Shen, and R. Prywes, “The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the er to the Golgi,” Journal of Biological Chemistry, vol. 277, no. 15, pp. 13045–13052, 2002. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Oyadomari and M. Mori, “Roles of CHOP/GADD153 in endoplasmic reticulum stress,” Cell Death & Differentiation, vol. 11, no. 4, pp. 381–389, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. S. J. Marciniak, C. Y. Yun, S. Oyadomari et al., “CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum,” Genes and Development, vol. 18, no. 24, pp. 3066–3077, 2004. View at Publisher · View at Google Scholar · View at Scopus
  91. Y. Wang, L. Vera, W. H. Fischer, and M. Montminy, “The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis,” Nature, vol. 460, no. 7254, pp. 534–537, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. G. S. Hotamisligil, “Endoplasmic reticulum stress and the inflammatory basis of metabolic disease,” Cell, vol. 140, no. 6, pp. 900–917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. D. Ron and P. Walter, “Signal integration in the endoplasmic reticulum unfolded protein response,” Nature Reviews Molecular Cell Biology, vol. 8, no. 7, pp. 519–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Fu, S. M. Watkins, and G. S. Hotamisligil, “The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling,” Cell Metabolism, vol. 15, no. 5, pp. 623–634, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. U. Özcan, Q. Cao, E. Yilmaz et al., “Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes,” Science, vol. 306, no. 5695, pp. 457–461, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. J. Lee and U. Ozcan, “Unfolded protein response signaling and metabolic diseases,” The Journal of Biological Chemistry, vol. 289, no. 3, pp. 1203–1211, 2014. View at Publisher · View at Google Scholar · View at Scopus
  97. X.-Q. Zhang, C.-F. Xu, C.-H. Yu, W.-X. Chen, and Y.-M. Li, “Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease,” World Journal of Gastroenterology, vol. 20, no. 7, pp. 1768–1776, 2014. View at Publisher · View at Google Scholar · View at Scopus
  98. C. Hetz, “The unfolded protein response: controlling cell fate decisions under ER stress and beyond,” Nature Reviews Molecular Cell Biology, vol. 13, no. 2, pp. 89–102, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. C. X. C. Santos, L. Y. Tanaka, J. Wosniak, and F. R. M. Laurindo, “Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase,” Antioxidants & Redox Signaling, vol. 11, no. 10, pp. 2409–2427, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. C. M. Haynes, E. A. Titus, and A. A. Cooper, “Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death,” Molecular Cell, vol. 15, no. 5, pp. 767–776, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. S. B. Cullinan and J. A. Diehl, “Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway,” International Journal of Biochemistry and Cell Biology, vol. 38, no. 3, pp. 317–332, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. J. D. Hayes and A. T. Dinkova-Kostova, “The Nrf2 regulatory network provides an interface between redox and intermediary metabolism,” Trends in Biochemical Sciences, vol. 39, no. 4, pp. 199–218, 2014. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Chowdhry, M. H. Nazmy, P. J. Meakin et al., “Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis,” Free Radical Biology and Medicine, vol. 48, no. 2, pp. 357–371, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Sugimoto, K. Okada, J. Shoda et al., “Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice,” The American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 298, no. 2, pp. G283–G294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. R. J. Kaufman, S. H. Back, B. Song, J. Han, and J. Hassler, “The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in beta-cells,” Diabetes, Obesity and Metabolism, vol. 12, no. 2, pp. 99–107, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. K. Zhang, “Integration of ER stress, oxidative stress and the inflammatory response in health and disease,” International Journal of Clinical and Experimental Medicine, vol. 3, no. 1, pp. 33–40, 2010. View at Google Scholar · View at Scopus
  107. R. A. Egnatchik, A. K. Leamy, D. A. Jacobson, M. Shiota, and J. D. Young, “ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload,” Molecular Metabolism, vol. 3, no. 5, pp. 544–553, 2014. View at Publisher · View at Google Scholar · View at Scopus
  108. A. K. Leamy, R. A. Egnatchik, M. Shiota et al., “Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells,” Journal of Lipid Research, vol. 55, no. 7, pp. 1478–1488, 2014. View at Publisher · View at Google Scholar · View at Scopus
  109. A. I. Cederbaum, Y. Lu, and D. Wu, “Role of oxidative stress in alcohol-induced liver injury,” Archives of Toxicology, vol. 83, no. 6, pp. 519–548, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Cichoz-Lach and A. Michalak, “Oxidative stress as a crucial factor in liver diseases,” World Journal of Gastroenterology, vol. 20, no. 25, pp. 8082–8091, 2014. View at Publisher · View at Google Scholar · View at Scopus
  111. A. I. Cederbaum, “Alcohol metabolism,” Clinics in Liver Disease, vol. 16, no. 4, pp. 667–685, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Ambade and P. Mandrekar, “Oxidative stress and inflammation: essential partners in alcoholic liver disease,” International Journal of Hepatology, vol. 2012, Article ID 853175, 9 pages, 2012. View at Publisher · View at Google Scholar
  113. A. Louvet and P. Mathurin, “Alcoholic liver disease: mechanisms of injury and targeted treatment,” Nature Reviews Gastroenterology & Hepatology, vol. 12, no. 4, pp. 231–242, 2015. View at Publisher · View at Google Scholar
  114. C. S. Lieber, “Alcohol: its metabolism and interaction with nutrients,” Annual Review of Nutrition, vol. 20, pp. 395–430, 2000. View at Publisher · View at Google Scholar · View at Scopus
  115. C. S. Lieber, “Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis,” Alcohol, vol. 34, no. 1, pp. 9–19, 2004. View at Publisher · View at Google Scholar · View at Scopus
  116. Y. Lu and A. I. Cederbaum, “CYP2E1 and oxidative liver injury by alcohol,” Free Radical Biology and Medicine, vol. 44, no. 5, pp. 723–738, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. T. Hügle, F. Fehrmann, E. Bieck et al., “The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein,” Virology, vol. 284, no. 1, pp. 70–81, 2001. View at Publisher · View at Google Scholar · View at Scopus
  118. L. Kong, S. Li, M. Huang et al., “The roles of endoplasmic reticulum overload response induced by HCV and NS4B protein in human hepatocyte viability and virus replication,” PLOS ONE, vol. 10, no. 4, Article ID e0123190, 2015. View at Publisher · View at Google Scholar
  119. C. Vasallo and P. Gastaminza, “Cellular stress responses in hepatitis C virus infection: mastering a two-edged sword,” Virus Research, 2015. View at Publisher · View at Google Scholar
  120. Y. Li, D. F. Boehning, T. Qian, V. L. Popov, and S. A. Weinman, “Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity,” The FASEB Journal, vol. 21, no. 10, pp. 2474–2485, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. G. Gong, G. Waris, R. Tanveer, and A. Siddiqui, “Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-κB,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9599–9604, 2001. View at Publisher · View at Google Scholar · View at Scopus
  122. S. Li, L. Ye, X. Yu et al., “Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation,” Virology, vol. 391, no. 2, pp. 257–264, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. K. Awe, C. Lambert, and R. Prange, “Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein,” FEBS Letters, vol. 582, no. 21-22, pp. 3179–3184, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Dodson, V. Darley-Usmar, and J. Zhang, “Cellular metabolic and autophagic pathways: traffic control by redox signaling,” Free Radical Biology and Medicine, vol. 63, pp. 207–221, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. R. Scherz-Shouval, E. Shvets, E. Fass, H. Shorer, L. Gil, and Z. Elazar, “Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4,” The EMBO Journal, vol. 26, no. 7, pp. 1749–1760, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. Y. Chen, M. B. Azad, and S. B. Gibson, “Superoxide is the major reactive oxygen species regulating autophagy,” Cell Death and Differentiation, vol. 16, no. 7, pp. 1040–1052, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. S. P. Elmore, T. Qian, S. F. Grissom, and J. J. Lemasters, “The mitochondrial permeability transition initiates autophagy in rat hepatocytes,” The FASEB Journal, vol. 15, no. 12, pp. 2286–2287, 2001. View at Google Scholar · View at Scopus
  128. A. Takamura, M. Komatsu, T. Hara et al., “Autophagy-deficient mice develop multiple liver tumors,” Genes and Development, vol. 25, no. 8, pp. 795–800, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. K. K. Kharbanda, D. L. McVicker, R. K. Zetterman, and T. M. Donohue Jr., “Ethanol consumption reduces the proteolytic capacity and protease activities of hepatic lysosomes,” Biochimica et Biophysica Acta, vol. 1245, no. 3, pp. 421–429, 1995. View at Publisher · View at Google Scholar · View at Scopus
  130. K. K. Kharbanda, D. L. McVicker, R. K. Zetterman, and T. M. Donohue Jr., “Ethanol consumption alters trafficking of lysosomal enzymes and affects the processing of procathepsin L in rat liver,” Biochimica et Biophysica Acta: General Subjects, vol. 1291, no. 1, pp. 45–52, 1996. View at Publisher · View at Google Scholar · View at Scopus
  131. T. M. Donohue, T. V. Curry-McCoy, A. A. Nanji et al., “Lysosomal leakage and lack of adaptation of hepatoprotective enzyme contribute to enhanced susceptibility to ethanol-induced liver injury in female rats,” Alcoholism: Clinical and Experimental Research, vol. 31, no. 11, pp. 1944–1952, 2007. View at Publisher · View at Google Scholar · View at Scopus
  132. Y. Li, S. Wang, H. Ni, H. Huang, and W. Ding, “Autophagy in alcohol-induced multiorgan injury: mechanisms and potential therapeutic targets,” BioMed Research International, vol. 2014, Article ID 498491, 20 pages, 2014. View at Publisher · View at Google Scholar
  133. W. X. Ding, M. Li, X. Chen et al., “Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice,” Gastroenterology, vol. 139, no. 5, pp. 1740–1752, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. P. G. Thomes, C. S. Trambly, G. M. Thiele et al., “Proteasome activity and autophagosome content in liver are reciprocally regulated by ethanol treatment,” Biochemical and Biophysical Research Communications, vol. 417, no. 1, pp. 262–267, 2012. View at Publisher · View at Google Scholar · View at Scopus
  135. D. Wu, X. Wang, R. Zhou, L. Yang, and A. I. Cederbaum, “Alcohol steatosis and cytotoxicity: the role of cytochrome P4502E1 and autophagy,” Free Radical Biology and Medicine, vol. 53, no. 6, pp. 1346–1357, 2012. View at Publisher · View at Google Scholar · View at Scopus
  136. C.-W. Lin, H. Zhang, M. Li et al., “Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice,” Journal of Hepatology, vol. 58, no. 5, pp. 993–999, 2013. View at Publisher · View at Google Scholar · View at Scopus
  137. A. Dolganiuc, P. G. Thomes, W.-X. Ding, J. J. Lemasters, and T. M. Donohue Jr., “Autophagy in alcohol-induced liver diseases,” Alcoholism: Clinical and Experimental Research, vol. 36, no. 8, pp. 1301–1308, 2012. View at Publisher · View at Google Scholar · View at Scopus
  138. P. Jiang, Z. Huang, H. Zhao, and T. Wei, “Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease,” Biochemical and Biophysical Research Communications, vol. 433, no. 4, pp. 408–414, 2013. View at Publisher · View at Google Scholar · View at Scopus
  139. X. Zhang and J. J. Lemastersn, “Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes,” Free Radical Biology and Medicine, vol. 63, pp. 243–253, 2013. View at Publisher · View at Google Scholar · View at Scopus
  140. M. A. Krenn, M. Schürz, B. Teufl, K. Uchida, P. M. Eckl, and N. Bresgen, “Ferritin-stimulated lipid peroxidation, lysosomal leak, and macroautophagy promote lysosomal ‘metastability’ in primary hepatocytes determining in vitro cell survival,” Free Radical Biology and Medicine, vol. 80, pp. 48–58, 2015. View at Publisher · View at Google Scholar · View at Scopus
  141. J. K. Ready and G. P. Mannaerts, “Peroxisomal lipid metabolism,” Annual Review of Nutrition, vol. 14, pp. 343–370, 1994. View at Publisher · View at Google Scholar · View at Scopus
  142. P. A. Loughran, D. B. Stolz, Y. Vodovotz, S. C. Watkins, R. L. Simmons, and T. R. Billiar, “Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 13837–13842, 2005. View at Publisher · View at Google Scholar · View at Scopus
  143. M. Schrader and H. D. Fahimi, “Peroxisomes and oxidative stress,” Biochimica et Biophysica Acta, vol. 1763, no. 12, pp. 1755–1766, 2006. View at Publisher · View at Google Scholar · View at Scopus
  144. R. J. A. Wanders, P. Vreken, S. Ferdinandusse et al., “Peroxisomal fatty acid α- and β-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases,” Biochemical Society Transactions, vol. 29, no. 2, pp. 250–267, 2001. View at Publisher · View at Google Scholar · View at Scopus
  145. J. K. Reddy, “Peroxisome proliferators and peroxisome proliferator-activated receptor α: biotic and xenobiotic sensing,” American Journal of Pathology, vol. 164, no. 6, pp. 2305–2321, 2004. View at Publisher · View at Google Scholar · View at Scopus
  146. B. Knebel, S. Hartwig, J. Haas et al., “Peroxisomes compensate hepatic lipid overflow in mice with fatty liver,” Biochimica et Biophysica Acta, vol. 1851, no. 7, pp. 965–976, 2015. View at Publisher · View at Google Scholar
  147. J. C. Collins, I. H. Scheinberg, D. R. Giblin, and I. Sternlieb, “Hepatic peroxisomal abnormalities in abetalipoproteinemia,” Gastroenterology, vol. 97, no. 3, pp. 766–770, 1989. View at Google Scholar · View at Scopus
  148. S. Yu, S. Rao, and J. K. Reddy, “Peroxisome proliferator-activated receptors, fatty acid oxidation, steatohepatitis and hepatocarcinogenesis,” Current Molecular Medicine, vol. 3, no. 6, pp. 561–572, 2003. View at Publisher · View at Google Scholar · View at Scopus
  149. R. Dirkx, I. Vanhorebeek, K. Martens et al., “Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities,” Hepatology, vol. 41, no. 4, pp. 868–878, 2005. View at Publisher · View at Google Scholar · View at Scopus
  150. N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich, “Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species,” Physiological Reviews, vol. 89, no. 1, pp. 27–71, 2009. View at Publisher · View at Google Scholar · View at Scopus
  151. B. J. Goldstein, K. Mahadev, X. Wu, L. Zhu, and H. Motoshima, “Role of insulin-induced reactive oxygen species in the insulin signaling pathway,” Antioxidants and Redox Signaling, vol. 7, no. 7-8, pp. 1021–1031, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. J. Kwon, S.-R. Lee, K.-S. Yang et al., “Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 47, pp. 16419–16424, 2004. View at Publisher · View at Google Scholar · View at Scopus
  153. S.-R. Lee, K.-S. Yang, J. Kwon, C. Lee, W. Jeong, and S. G. Rhee, “Reversible inactivation of the tumor suppressor PTEN by H2O2,” The Journal of Biological Chemistry, vol. 277, no. 23, pp. 20336–20342, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. T. Fiaschi, F. Buricchi, G. Cozzi et al., “Redox-dependent and ligand-independent trans-activation of insulin receptor by globular adiponectin,” Hepatology, vol. 46, no. 1, pp. 130–139, 2007. View at Publisher · View at Google Scholar · View at Scopus
  155. S. Iwakami, H. Misu, T. Takeda et al., “Concentration-dependent dual effects of hydrogen peroxide on insulin signal transduction in H4IIEC hepatocytes,” PLoS ONE, vol. 6, no. 11, Article ID e27401, 2011. View at Publisher · View at Google Scholar · View at Scopus
  156. K. A. Robinson, C. A. Stewart, Q. N. Pye et al., “Redox-sensitive protein phosphatase activity regulates the phosphorylation state of p38 protein kinase in primary astrocyte culture,” Journal of Neuroscience Research, vol. 55, no. 6, pp. 724–732, 1999. View at Publisher · View at Google Scholar · View at Scopus
  157. H. Kamata, S.-I. Honda, S. Maeda, L. Chang, H. Hirata, and M. Karin, “Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases,” Cell, vol. 120, no. 5, pp. 649–661, 2005. View at Publisher · View at Google Scholar · View at Scopus
  158. C. C. Wentworth, A. Alam, R. M. Jones, A. Nusrat, and A. S. Neish, “Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase,” The Journal of Biological Chemistry, vol. 286, no. 44, pp. 38448–38455, 2011. View at Publisher · View at Google Scholar · View at Scopus
  159. S. R. Lee, K. S. Kwon, S. R. Kim, and S. G. Rhee, “Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor,” The Journal of Biological Chemistry, vol. 273, pp. 15366–15372, 1998. View at Publisher · View at Google Scholar
  160. S. Boura-Halfon and Y. Zick, “Phosphorylation of IRS proteins, insulin action, and insulin resistance,” American Journal of Physiology: Endocrinology and Metabolism, vol. 296, no. 4, pp. E581–E591, 2009. View at Publisher · View at Google Scholar · View at Scopus
  161. H. Bai, W. Zhang, X. Qin et al., “Hydrogen peroxide modulates the proliferation/quiescence switch in the liver during embryonic development and posthepatectomy regeneration,” Antioxidants & Redox Signaling, vol. 22, no. 11, pp. 921–937, 2015. View at Publisher · View at Google Scholar
  162. E. R. Galimov, “The role of p66shc in oxidative stress and apoptosis,” Acta Naturae, vol. 2, no. 4, pp. 44–51, 2010. View at Google Scholar
  163. G. Xi, X.-C. Shen, C. Wai, and D. R. Clemmons, “Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I,” Journal of Biological Chemistry, vol. 288, no. 22, pp. 15641–15653, 2013. View at Publisher · View at Google Scholar · View at Scopus
  164. O. Sergent, M. Pereira, C. Belhomme, M. Chevanne, L. Huc, and D. Lagadic-Gossmann, “Role for membrane fluidity in ethanol-induced oxidative stress of primary rat hepatocytes,” Journal of Pharmacology and Experimental Therapeutics, vol. 313, no. 1, pp. 104–111, 2005. View at Publisher · View at Google Scholar · View at Scopus
  165. P. Nourissat, M. Travert, M. Chevanne et al., “Ethanol induces oxidative stress in primary rat hepatocytes through the early involvement of lipid raft clustering,” Hepatology, vol. 47, no. 1, pp. 59–70, 2008. View at Publisher · View at Google Scholar · View at Scopus
  166. F. Aliche-Djoudi, N. Podechard, A. Collin et al., “A role for lipid rafts in the protection afforded by docosahexaenoic acid against ethanol toxicity in primary rat hepatocytes,” Food and Chemical Toxicology, vol. 60, pp. 286–296, 2013. View at Publisher · View at Google Scholar · View at Scopus
  167. A. Collin, K. Hardonnière, M. Chevanne et al., “Cooperative interaction of benzo[a]pyrene and ethanol on plasma membrane remodeling is responsible for enhanced oxidative stress and cell death in primary rat hepatocytes,” Free Radical Biology and Medicine, vol. 72, pp. 11–22, 2014. View at Publisher · View at Google Scholar · View at Scopus
  168. J. Woudenberg, K. P. Rembacz, M. Hoekstra et al., “Lipid rafts are essential for peroxisome biogenesis in HepG2 cells,” Hepatology, vol. 52, no. 2, pp. 623–633, 2010. View at Publisher · View at Google Scholar · View at Scopus
  169. A. P. Arruda, B. M. Pers, G. Parlakgül, E. Güney, K. Inouye, and G. S. Hotamisligil, “Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity,” Nature Medicine, vol. 20, pp. 1427–1435, 2014. View at Publisher · View at Google Scholar · View at Scopus