BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Heme Oxygenase-1 as a Potential Therapeutic Target for Hepatoprotection

  • Farombi, Ebenezer Olatunde (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Surh, Young-Joon (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
  • Accepted : 2006.08.11
  • Published : 2006.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

Keywords

References

  1. Abe, T., Yamamoto, O., Gotoh, S., Yan, Y., Todaka, N. and Higashi, K. (2000) Cadmium-induced mRNA expression of Hsp32 is augmented in metallothionein-I and -II knock-out mice. Arch. Biochem. Biophys. 382, 81-88. https://doi.org/10.1006/abbi.2000.1997
  2. Alam, J., Shibahara, S. and Smith, A. (1989) Transcriptional activation of the heme oxygenase gene by heme and cadmium in mouse hepatoma cells. J. Biol. Chem. 264, 6371-6375.
  3. Aleksunes, L. M., Slitt, A. M., Cherrington, N. J., Thibodeau, M. S., Klaassen, C. D. and Manautou, J. E. (2005) Differential expression of mouse hepatic transporter genes in response to acetaminophen and carbon tetrachloride. Toxicol. Sci. 83, 44-52. https://doi.org/10.1093/toxsci/kfi013
  4. Amersi, F., Buelow, R., Kato, H., Ke, B., Coito, A. J., Shen, X. D., Zhao, D., Zaky, J., Melinek, J., Lassman, C. R., Kolls, J. K., Alam, J., Ritter, T., Volk, H. D., Farmer, D. G., Ghobrial, R. M., Busuttil, R. W. and Kupiec-Weglinski, J. W. (1999) Up regulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J. Clin. Invest. 104, 1631-1639. https://doi.org/10.1172/JCI7903
  5. Amersi, F., Shen, X. D., Anselmo, D., Melinek, J., Iyer, S., Southard, D. J., Katori, M., Volk, H. D., Busuttil, R. W., Buelow, R. and Kupiec-Weglinski, J. W. (2002) Ex vivo exposure to carbon monoxide prevents hepatic ischemia/ reperfusion injury through p38 MAP kinase pathway. Hepatology 35, 815-823. https://doi.org/10.1053/jhep.2002.32467
  6. Awad, J. A., Horn, J. L., Roberts, L. J 2$^{nd}$ and Franks J. J. (1996). Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprostanes. Anesthesiology. 84, 910-916. https://doi.org/10.1097/00000542-199604000-00019
  7. Balla, G., Jacob, H.S., Balla, J., Rosenberg, M., Nath, K., Apple, F., Eaton, J. W. and Vercellotti, G. M. (1992) Ferritin: a cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267, 18148-18153.
  8. Baranano, D. E., Rao, M., Ferris, C. D. and Snyder, S. H. (2002) Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl. Acad. Sci. USA 99, 16093-16098. https://doi.org/10.1073/pnas.252626999
  9. Bauer, I., Vollmar, B., Jaeschke, H., Rensing, H., Kraemer, T., Larsen, R. and Bauer, M. (2000) Transcriptional activation of heme oxygenase-1 and its functional significance in acetaminophen-induced hepatitis and hepatocellular injury in the rat. J. Hepatol. 33, 395-406. https://doi.org/10.1016/S0168-8278(00)80275-5
  10. Bauer, I., Wanner,. G. A., Rensing, H., Alte, C., Miescher, E. A., Wolf, B., Pannen, B. H., Clemens, M. G. and Bauer, M. (1998) Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Hepatology 27, 829-838. https://doi.org/10.1002/hep.510270327
  11. Bauer, M., Pannen, B. H., Bauer, I., Herzog, C., Wanner, G. A, Hanselmann, R., Zhang, J. X., Clemens, M. G. and Larsen, R. (1996) Evidence for a functional link between stress response and vascular control in hepatic portal circulation. Am. J. Physiol. 271, 929-935. https://doi.org/10.1152/ajpcell.1996.271.3.C929
  12. Brouard, S., Berberat, P. O., Tobiasch, E., Seldon, M. P., Bach, F. H. and Soares, M. P. (2002) Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor NFkappa B to protect endothelial cells from tumor necrosis factoralpha-mediated apoptosis. J. Biol. Chem. 277, 17950-17961. https://doi.org/10.1074/jbc.M108317200
  13. Brown, J. L., Kitchin, K. T. and George M. (1997) Dimethylarsenic acid treatment alters six different rat biochemical parameters: relevance to arsenic carcinogenesis. Teratog. Carcinog. Mutagen. 17, 71-84. https://doi.org/10.1002/(SICI)1520-6866(1997)17:2<71::AID-TCM3>3.0.CO;2-B
  14. Brune, B. and Ullrich, V. (1987) Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol. Pharmacol. 32, 497-504.
  15. Buzaleh, A. M. and Batlle, A. M. (2005) Glutathione depletion and anaesthesia in mice alter heme and drug metabolizing enzymes. Biochim. Biophys. Acta. 1723, 128-134. https://doi.org/10.1016/j.bbagen.2005.01.007
  16. Cavigelli, M., Li, W. W., Lin, A., Su, B., Yoshioka, K. and Karin, M. (1996) The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase. EMBO J. 15, 6269-6279.
  17. Chapin, J. W., Newland, M. C. and Hurlbert, B. J. (1989) Anesthesia for liver transplantation. Semin Liver Dis. 9, 195-201. https://doi.org/10.1055/s-2008-1040513
  18. Chen, C., Pung, D., Leong, V., Hebbar, V., Shen, G., Nair, S., Li, W. and Kong, A. N. (2004) Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals. Free Radic. Biol. Med. 37, 1578-1590. https://doi.org/10.1016/j.freeradbiomed.2004.07.021
  19. Chen, G. G., Liu, Z. M., Vlantis, A. C, Tse, G. M., Leung, B. C. and van Hasselt, C. A. (2004) Heme oxygenase-1 protects against apoptosis induced by tumor necrosis factor-alpha and cycloheximide in papillary thyroid carcinoma cells. J. Cell. Biochem. 92, 1246-1256. https://doi.org/10.1002/jcb.20157
  20. Chiu, H., Brittingham, J. A. and Laskin, D. L. (2002) Differential induction of heme oxygenase-1 in macrophages and hepatocytes during acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin. Toxicol. Appl. Pharmacol. 181, 106-115. https://doi.org/10.1006/taap.2002.9409
  21. Christova, T. Y., Duridanova, D. B. and Setchenska, M. S. (2002) Enhanced heme oxygenase activity increases the antioxidant defense capacity of guinea pig liver upon acute cobalt chloride loading: comparison with rat liver. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 131, 177-184. https://doi.org/10.1016/S1532-0456(01)00287-3
  22. Coceani, F., Kelsey, L., Seidlitz, E., Marks, G. S., McLaughlin, B. E., Vreman, H. J., Stevenson, D. K., Rabinovitch, M. and Ackerley, C. (1997) Carbon monoxide formation in the ductus arteriosus in the lamb: implications for the regulation of muscle tone. Br. J. Pharmacol. 120, 599-608. https://doi.org/10.1038/sj.bjp.0700947
  23. De Groot, H. and Sies, H. (1989) Cytochrome P-450, reductive metabolism, and cell injury. Drug Metab. Rev. 20, 275-284. https://doi.org/10.3109/03602538909103543
  24. Dorman, R. B., Bajt, M. L., Farhood, A., Mayes, J. and Jaeschke, H. (2004) Heme oxygenase-1 induction in hepatocytes and non-parenchymal cells protects against liver injury during endotoxemia. Comp. Hepatol. 3, 42. https://doi.org/10.1186/1476-5926-2-S1-S42
  25. Dorman, R. B., Wunder, C. and Brock, R. W. (2005) Cobalt protoporphyrin protects against hepatic parenchymal injury and microvascular dysfunction during experimental rhabdomyolysis. Shock. 23, 275-280.
  26. Eisenstein, R. S., Garcia-Mayol, D., Pettingell, W. and Munro, H. N. (1991) Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. Proc. Natl. Acad. Sci. USA 88, 688-692. https://doi.org/10.1073/pnas.88.3.688
  27. Elbirt, K. K., Whitmarsh, A. J., Davis, R. J. and Bonkovsky, H. L. (1998) Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells. Role of mitogenactivated protein kinases. J. Biol. Chem. 273, 8922-8931. https://doi.org/10.1074/jbc.273.15.8922
  28. Fang, J., Akaike, T. and Maeda, H. (2004) Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis. 9, 27-35. https://doi.org/10.1023/B:APPT.0000012119.83734.4e
  29. Ferris, C. D., Jaffrey, S. R., Sawa, A., Takahashi, M., Brady, S. D., Barrow, R. K., Tysoe, S. A., Wolosker, H., Baranano. D. E., Dore, S., Poss, K. D. and Snyder, S. H. (1999) Haem oxygenase-1 prevents cell death by regulating cellular iron. Nat. Cell. Biol. 1, 152-157. https://doi.org/10.1038/11072
  30. Fondevila, C., Shen, X. D., Tsuchiyashi, S., Yamashita, K., Csizmadia, E., Lassman, C., Busuttil, R. W., Kupiec-Weglinski, J. W. and Bach, F. H. (2004) Biliverdin therapy protects rat livers from ischemia and reperfusion injury. Hepatology 40, 1333-1341. https://doi.org/10.1002/hep.20480
  31. Fujii, H., Takahashi, T., Nakahira, K., Uehara, K., Shimizu, H., Matsumi, M., Morita, K., Hirakawa, M., Akagi, R. and Sassa, S. (2003) Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis. Crit. Care Med. 31, 893-902. https://doi.org/10.1097/01.CCM.0000050442.54044.06
  32. Gabis, K. K., Gildemeister, O. S., Pepe, J. A., Lambrecht, R. W and Bonkovsky, H. L. (1996) Induction of heme oxygenase-1 in LMH cells. Comparison of LMH cells to primary cultures of chick embryo liver cells. Biochim. Biophys. Acta 1290, 113-120. https://doi.org/10.1016/0304-4165(96)00009-8
  33. Gardner, C. R., Heck, D. E., Yang, C. S., Thomas, P. E, Zhang, X. J., DeGeorge, G. L., Laskin, J. D. and Laskin, D. L. (1998) Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat. Hepatology 27, 748-754. https://doi.org/10.1002/hep.510270316
  34. Germain, E., Chevalier, J., Siess, M. H. and Teyssier, C. (2003) Hepatic metabolism of diallyl disulphide in rat and man. Xenobiotica 33, 1185-1199. https://doi.org/10.1080/00498250310001636840
  35. Gill, R. Q, and Sterling, R. K. (2001) Acute liver failure. J. Clin. Gastroenterol. 33, 191-198. https://doi.org/10.1097/00004836-200109000-00005
  36. Goda, N., Suzuki, K., Naito, M., Takeoka, S., Tsuchida, E., Ishimura, Y., Tamatani, T. and Suematsu, M. (1998) Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. J. Clin. Invest. 101, 604-612. https://doi.org/10.1172/JCI1324
  37. Goldring, C. E., Kitteringham, N. R., Elsby. R., Randle, L. E., Clement, Y. N. and Williams, D. P., McMahon, M., Hayes, J.D., Itoh, K., Yamamoto, M. and Park, B.K. (2004) Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice. Hepatology. 39, 1267-1276. https://doi.org/10.1002/hep.20183
  38. Gong, P., Hu, B. and Cederbaum, A. I. (2004) Diallyl sulfide induces heme oxygenase-1 through MAPK pathway. Arch. Biochem. Biophys. 432, 252-260. https://doi.org/10.1016/j.abb.2004.09.024
  39. Gonzales, S., Polizio, A. H., Erario, M. A. and Tomaro, M. L. (2005) Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver. World J. Gastroenterol. 11, 3533-3538. https://doi.org/10.3748/wjg.v11.i23.3533
  40. Gonzales, S., Polizio, A. H., Erario, M. A. and Tomaro, M. L. (2005) Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver. World J.Gastroenterol. 11, 3533-3538. https://doi.org/10.1016/j.bbrc.2003.12.089
  41. Grosser, N., Oberle, S., Berndt, G., Erdmann, K., Hemmerle, A. and Schroder, H. (2004) Antioxidant action of L-alanine: heme oxygenase-1 and ferritin as possible mediators. Biochem. Biophys. Res. Commun. 314, 351-355. https://doi.org/10.1016/j.bbrc.2003.12.089
  42. Guyonnet, D., Siess, M. H., Le Bon, A. M. and Suschetet, M. (1999) Modulation of phase II enzymes by organosulfur compounds from allium vegetables in rat tissues. Toxicol. Appl. Pharmacol. 154, 50-58. https://doi.org/10.1006/taap.1998.8574
  43. He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. and Alam, J. (2001) Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J. Biol. Chem. 276, 20858-20865. https://doi.org/10.1074/jbc.M101198200
  44. Herman-Antosiewicz, A. and Singh, S. V. (2004) Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review. Mutat. Res. 555, 121-131. https://doi.org/10.1097/00000542-200211000-00043
  45. Hoetzel, A., Geiger, S., Loop, T., Welle, A., Schmidt, R., Humar, M., Pahl, H. L., Geiger, K. K. and Pannen B. H. (2002) Differential effects of volatile anesthetics on hepatic heme oxygenase-1 expression in the rat. Anesthesiology 97, 1318-1321. https://doi.org/10.1097/00000542-200211000-00043
  46. Hoetzel, A., Leitz, D., Schmidt, R., Tritschler, E., Bauer, I., Loop, T., Humar, M., Geiger, K. K. and Pannen, B. H. (2006) Mechanism of hepatic heme oxygenase-1 induction by isoflurane. Anesthesiology, 104, 101-109. https://doi.org/10.1097/00000542-200601000-00016
  47. Immenschuh, S., Kietzmann, T., Hinke, V., Wiederhold, M., Katz, N. and Muller-Eberhard, U. (1998) The rat heme oxygenase-1 gene is transcriptionally induced via the protein kinase A signaling pathway in rat hepatocyte cultures. Mol. Pharmacol. 53, 483-491. https://doi.org/10.1021/bi00041a018
  48. Immenschuh, S., Iwahara, S., Satoh, H., Nell, C., Katz, N. and Muller-Eberhard, U. (1995) Expression of the mRNA of hemebinding protein 23 is coordinated with that of heme oxygenase-1 by heme and heavy metals in primary rat hepatocytes and hepatoma cells. Biochemistry 34, 13407-13411. https://doi.org/10.1021/bi00041a018
  49. Ishikawa, K., Takeuchi, N., Takahashi, S., Matera, K. M., Sato, M., Shibahara, S., Rousseau, D. L., Ikeda-Saito, M. and Yoshida, T. (1995) Heme oxygenase-2. Properties of the heme complex of the purified tryptic fragment of recombinant human heme oxygenase-2. J. Biol. Chem. 270, 6345-6350. https://doi.org/10.1074/jbc.270.11.6345
  50. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M. and Nabeshima, Y. (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236, 313-322. https://doi.org/10.1006/bbrc.1997.6943
  51. Jacobs, J. M., Marek, D., Walton, H. S., Sinclair, P. R. and Sinclair, J. F. (1999) Effect of sodium arsenite on heme metabolism in cultured chick embryo hepatocytes. Arch. Biochem. Biophys. 371, 8-14. https://doi.org/10.1006/abbi.1999.1416
  52. Janssen, Y. M., Marsh, J. P., Absher, M. P., Gabrielson, E., Borm, P. J., Driscoll, K. and Mossman, B. T. (1994) Oxidant stress responses in human pleural mesothelial cells exposed to asbestos. Am. J. Respir. Crit. Care Med. 149, 795-802. https://doi.org/10.1164/ajrccm.149.3.8118652
  53. Jeong, W. S, Keum, Y. S, Chen, C., Jain, M. R., Shen, G., Kim, J. H., Li, W. and Kong, A. N. (2005) Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J. Biochem. Mol. Biol. 38, 167-176. https://doi.org/10.1023/A:1002889814723
  54. Kaliman, P. A., Nikitchenko, I. V., Sokol, O. A. and Strel'chenko, E. V. (2001) Regulation of heme oxygenase activity in rat liver during oxidative stress induced by cobalt chloride and mercury chloride. Biochemistry (Mosc). 66, 77-82. https://doi.org/10.1023/A:1002889814723
  55. Karin, M., Liu, Z. and Zandi, E. (1997) AP-1 function and regulation. Curr. Opin. Cell. Biol. 9, 240-246. https://doi.org/10.1016/S0955-0674(97)80068-3
  56. Kato, H., Amersi, F., Buelow, R., Melinek, J., Coito, A. J., Ke, B., Busuttil, R. W. and Kupiec-Weglinski, J. W. (2001) Heme oxygenase-1 overexpression protects rat livers from ischemia/ reperfusion injury with extended cold preservation. Am. J. Transplant. 1, 121-128. https://doi.org/10.1034/j.1600-6143.2001.10205.x
  57. Kawashima, A., Oda, Y., Yachie, A., Koizumi, S. and Nakanishi, I. (2002) Heme oxygenase-1 deficiency: the first autopsy case. Hum. Pathol. 33, 125-130. https://doi.org/10.1053/hupa.2002.30217
  58. Kenna, J. G. and Jones, R. M. (1995) The organ toxicity of inhaled anesthetics. Anesth Analg. 81, 51-66. https://doi.org/10.1097/00000539-199512001-00008
  59. Kensler, T. W. (1997) Chemoprevention by inducers of carcinogen detoxication enzymes. Environ. Health Perspect. 105, 965-970. https://doi.org/10.2307/3433311
  60. Keyse, S. M. and Tyrrell, R. M. (1989) Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc. Natl. Acad. Sci. USA 86, 99-103. https://doi.org/10.1196/annals.1329.061
  61. Kim, E. H., Kim, D. H., Na, H. K. and Surh, Y. J. (2004) Effects of Cyclopentenone Prostaglandins on the Expression of Heme Oxygenase-1 in MCF-7 Cells. Ann. N. Y. Acad. Sci. 1030, 493-500 https://doi.org/10.1196/annals.1329.061
  62. Kitchin, K. T., Del Razo, L. M., Brown, J. L., Anderson, W. L. and Kenyon, E. M. (1999) An integrated pharmacokinetic and pharmacodynamic study of arsenite action. 1. Heme oxygenase induction in rats. Teratog. Carcinog. Mutagen. 19, 385-402. https://doi.org/10.1002/(SICI)1520-6866(1999)19:6<385::AID-TCM3>3.0.CO;2-V
  63. Kwak, M. K., Wakabayashi, N. and Kensler, T. W. (2004) Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers. Mutat. Res. 555, 133-148. https://doi.org/10.1053/gast.2001.23249
  64. Kyokane, T., Norimizu, S., Taniai, H., Yamaguchi, T., Takeoka, S., Tsuchida, E., Naito, M., Nimura, Y., Ishimura, Y. and Suematsu, M. (2001) Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver. Gastroenterology 120, 1227-1240. https://doi.org/10.1053/gast.2001.23249
  65. Langouet, S., Furge, L. L, Kerriguy, N., Nakamura, K., Guillouzo, A. and Guengerich, F. P. (2000) Inhibition of human cytochrome P450 enzymes by 1,2-dithiole-3-thione, oltipraz and its derivatives, and sulforaphane. Chem. Res. Toxicol. 13, 245-252. https://doi.org/10.1021/tx990189w
  66. Laskin, D. L., Gardner, C. R., Price, V. F. and Jollow, D. J. (1995) Modulation of macrophage functioning abrogates the acute hepatotoxicity of acetaminophen. Hepatology 21, 1045-1050. https://doi.org/10.1002/hep.1840210424
  67. Lavrovsky, Y., Song, C. S., Chatterjee, B. and Roy, A. K. (2000) Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NF-kappa B. Mech. Ageing Dev. 114, 49-60. https://doi.org/10.1016/S0047-6374(00)00087-7
  68. Lee J-S and Surh Y-J. (2005).Nrf2 as a molecular target for chemoprevention. Cancer Lett. 224, 171-184. https://doi.org/10.1016/j.canlet.2004.09.042
  69. Li, P, Jiang H, Yang L, Quan S, Dinocca S, Rodriguez F, Abraham, N.G and Nasjletti, A. (2004) Angiotensin II induces carbon monoxide production in the perfused kidney: relationship to protein kinase C activation. Am. J. Physiol. Renal. Physiol. 287, 914-920. https://doi.org/10.1152/ajprenal.00073.2004
  70. Lin, J. H., Villalon, P., Martasek, P. and Abraham, N. G. (1990) Regulation of heme oxygenase gene expression by cobalt in rat liver and kidney. Eur. J. Biochem. 192, 577-582. https://doi.org/10.1111/j.1432-1033.1990.tb19263.x
  71. Liu, J., Kadiiska, M. B., Corton, J. C., Qu, W., Waalkes, M. P., Mason, R. P., Liu, Y. and Klaassen, C. D. (2002) Acute cadmium exposure induces stress-related gene expression in wild-type and metallothionein-I/II-null mice. Free Radic. Biol. Med. 32, 525-535. https://doi.org/10.1016/S0891-5849(01)00826-7
  72. He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. and Alam, J. (2001) Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J. Biol. Chem. 276, 20858-20865. https://doi.org/10.1074/jbc.M101198200
  73. Liu, Z. M., Chen, G. G., Ng, E. K., Leung, W. K., Sung, J. J. and Chung, S. C. (2004) Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells. Oncogene 23, 503-513. https://doi.org/10.1038/sj.onc.1207173
  74. Liu, Y., Guyton, K. Z, Gorospe, M., Xu, Q., Lee, J. C. and Holbrook, N. J. (1996) Differential activation of ERK, JNK/SAPK and P38/CSBP/RK MAP kinase family members during the cellular response to arsenite. Free Radic. Biol. Med. 21, 771-81. https://doi.org/10.1016/0891-5849(96)00176-1
  75. Llesuy, S. F and Tomaro, M. L. (1994) Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochim. Biophys. Acta. 1223, 9-14. https://doi.org/10.1016/0167-4889(94)90067-1
  76. Lu, T. H, Shan, Y., Pepe, J., Lambrecht, R. W. and Bonkovsky, H. L. (2000) Upstream regulatory elements in chick heme oxygenase-1 promoter: a study in primary cultures of chick embryo liver cells. Mol. Cell. Biochem. 209, 17-27. https://doi.org/10.1023/A:1007025505842
  77. Lu, T. H., Pepe, J. A., Gildemeister, O. S., Tyrrell, R. M. and Bonkovsky, H. L. (1997) Regulation of expression of the human heme oxygenase-1 gene in transfected chick embryo liver cell cultures. Biochim. Biophys. Acta. 1352, 293-302. https://doi.org/10.1023/A:1007025505842
  78. Lu, T. H., Shan, Y., Pepe, J., Lambrecht, R. W. and Bonkovsky, H. L. (2000) Upstream regulatory elements in chick heme oxygenase-1 promoter: a study in primary cultures of chick embryo liver cells. Mol. Cell. Biochem. 209, 17-27. https://doi.org/10.1023/A:1007025505842
  79. Maeshima, H., Sato, M., Ishikawa, K., Katagata, Y. and Yoshida, T. (1996) Participation of altered upstream stimulatory factor in the induction of rat heme oxygenase-1 by cadmium. Nucleic Acids Res. 24, 2959-2965. https://doi.org/10.1093/nar/24.15.2959
  80. Maines, M. D. (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2, 2557-2568. https://doi.org/10.1089/ars.2005.7.1761
  81. Maines, M. D. (2005) The heme oxygenase sytem: Update 2005. Antiox Redox Signal 7, 1761-1766. https://doi.org/10.1089/ars.2005.7.1761
  82. Maines, M. D. and Gibbs, P. E. (2005) 30 some years of heme oxygenase: from a 'molecular wrecking ball' to a 'mesmerizing' trigger of cellular events. Biochem. Biophys. Res. Commun. 338, 568-577. https://doi.org/10.1016/j.bbrc.2005.08.121
  83. Maines, M. D., Trakshel, G. M. and Kutty, R. K. (1986) Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J. Biol. Chem. 261, 411-419.
  84. Makin, A. J. and Williams, R. (1997) Acetaminophen-induced hepatotoxicity: predisposing factors and treatments. Adv. Intern. Med. 42, 453-483. https://doi.org/10.1016/j.jhep.2004.11.040
  85. Malaguarnera, L., Madeddu, R., Palio, E., Arena, N. and Malaguarnera, M. (2005) Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients . J. Hepatol. 42, 585-591. https://doi.org/10.1016/j.jhep.2004.11.040
  86. Malstrom, S. E., Jekic-McMullen, D., Sambucetti, L., Ang, A., Reeves, R., Purchio, A. F., Contag, P. R. and West, D. B.(2004) In vivo bioluminescent monitoring of chemical toxicity using heme oxygenase-luciferase transgenic mice. Toxicol. Appl. Pharmacol. 200, 219-228. https://doi.org/10.1016/j.taap.2004.04.021
  87. Masini, E., Vannacci, A., Marzocca, C., Pierpaoli, S., Giannini, L., Fantappie, O., Mazzanti, R. and Mannaioni, P. F. (2003) Heme oxygenase-1 and the ischemia-reperfusion injury in the rat heart. Exp. Biol. Med. (Maywood). 228, 546-549. https://doi.org/10.1080/10739680490503384
  88. McCarter, S. D., Badhwar, A., Scott, J. R., Akyea, T. G., Bihari, A., Dungey, A. A., Harris, K. A. and Potter, R. F. (2004) Remote liver injury is attenuated by adenovirus-mediated gene transfer of heme oxygenase-1 during the systemic inflammatory response syndrome. Microcirculation 11, 587-595. https://doi.org/10.1080/10739680490503384
  89. McCoubrey, W. K Jr., Ewing, J. F. and Maines, M. D. (1992) Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal. Arch. Biochem. Biophys. 295, 13-20. https://doi.org/10.1016/0003-9861(92)90481-B
  90. McCoubrey, W. K. Jr., Huang, T. J. and Maines, M. D. (1997) Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur. J. Biochem. 247, 725-732. https://doi.org/10.1111/j.1432-1033.1997.00725.x
  91. McNally, S. J, Harrison, E. M., Ross, J. A., Garden, O. J. and Wigmore, S. J. (2006) Curcumin induces heme oxygenase-1 in hepatocytes and is protective in simulated cold preservation and warm reperfusion injury. Transplantation 81, 623-626. https://doi.org/10.1097/01.tp.0000184635.62570.13
  92. Michael, S. L., Pumford, N. R., Mayeux, P. R., Niesman, M. R. and Hinson, J. A. (1999) Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species. Hepatology. 30, 186-195. https://doi.org/10.1002/hep.510300104
  93. Milner, J. A. (2001) Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis. Adv. Exp. Med. Biol. 492, 69-81. https://doi.org/10.1016/0006-291X(90)91026-O
  94. Mitani, K., Fujita, H., Sassa, S. and Kappas, A. (1990) Activation of heme oxygenase and heat shock protein 70 genes by stress in human hepatoma cells. Biochem. Biophys. Res. Commun. 166, 1429-1434. https://doi.org/10.1016/0006-291X(90)91026-O
  95. Moore, B. A., Overhaus, M., Whitcomb, J., Ifedigbo, E., Choi, A. M., Otterbein, L. E. and Bauer, A. J (2005) Brief inhalation of low-dose carbon monoxide protects rodents and swine from postoperative ileus. Crit. Care Med. 33, 1317-1326. https://doi.org/10.1097/01.CCM.0000166349.76514.40
  96. Motterlini, R., Foresti, R., Bassi, R., Calabrese, V., Clark, J. E. and Green, C. J. (2000) Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric-oxide synthase and S-nitrosothiols. J. Biol. Chem. 275, 13613-13620. https://doi.org/10.1074/jbc.275.18.13613
  97. Munday, R. and Munday, C. M. (2004) Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds. J. Agric. Food Chem. 52, 1867-1871. https://doi.org/10.1021/jf030549s
  98. Nakahira, K., Takahashi, T., Shimizu, H., Maeshima, K., Uehara, K., Fujii, H., Nakatsuka, H., Yokoyama, M., Akagi, R. and Morita K. (2003) Protective role of heme oxygenase-1 induction in carbon tetrachloride-induced hepatotoxicity. Biochem. Pharmacol. 66, 1091-1105. https://doi.org/10.1016/S0006-2952(03)00444-1
  99. Nakaso K., Yano, H., Fukuhara, Y., Takeshima, T., Wada-Isoe, K. and Nakashima, K. (2003) PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins bby hemin in human neuroblastoma cells. FEBS Lett 546, 181-184. https://doi.org/10.1016/S0014-5793(03)00517-9
  100. Nelson, S. D. (1990) Molecular mechanisms of the hepatotoxicity caused by acetaminophen. Semin Liver Dis. 10, 267-278. https://doi.org/10.1055/s-2008-1040482
  101. Noriega, G. O., Ossola, J. O., Tomaro, M. L. and Batlle, A. M. (2000) Effect of acetaminophen on heme metabolism in rat liver. Int. J. Biochem. Cell. Biol. 32, 983-991. https://doi.org/10.1016/S1357-2725(00)00040-6
  102. Numazawa, S., Ishikawa, M., Yoshida, A., Tanaka, S. and Yoshida, T. (2003) A typical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress. Am. J. Physiol. Cell. Physiol. 285, 334-342. https://doi.org/10.1016/S0006-2952(99)00386-X
  103. Odaka, Y., Takahashi, T., Yamasaki, A., Suzuki, T., Fujiwara, T., Yamada, T., Hirakawa, M., Fujita, H., Ohmori, E. and Akagi, R. (2000) Prevention of halothane-induced hepatotoxicity by hemin pretreatment: protective role of heme oxygenase-1 induction. Biochem. Pharmacol. 59, 871-880. https://doi.org/10.1016/S0006-2952(99)00386-X
  104. Ossola, J. O. and Tomaro, M. L. (1998) Heme oxygenase induction by UVA radiation. A response to oxidative stress in rat liver. Int. J. Biochem. Cell. Biol. 30, 285-292. https://doi.org/10.1016/S1357-2725(97)00109-X
  105. Ossola, J. O., Groppa, M. D. and Tomaro, M. L. (1997) Relationship between oxidative stress and heme oxygenase induction by copper sulfate. Arch. Biochem. Biophys. 337, 332-337. https://doi.org/10.1006/abbi.1996.9788
  106. Otterbein, L., Chin, B. Y., Otterbein, S. L., Lowe, V. C., Fessler, H. E. and Choi, A. M. (1997) Mechanism of hemoglobininduced protection against endotoxemia in rats: a ferritinindependent pathway. Am. J. Physiol. 272, 268-275. https://doi.org/10.1016/S1471-4906(03)00181-9
  107. Otterbein, L. E., Soares, M. P., Yamashita, K. and Bach, F. H. (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 24, 449-455. https://doi.org/10.1016/S1471-4906(03)00181-9
  108. Pannen, B. H., Kohler, N., Hole, B., Bauer, M., Clemens, M. G. and Geiger, K. K. (1998) Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. J. Clin. Invest. 102, 1220-1228. https://doi.org/10.1172/JCI3428
  109. Pannen, B. H., Kohler, N., Hole, B., Bauer, M., Clemens, M. G., and Geiger, K. K. (1998) Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. J. Clin. Invest. 102, 1220-1228. https://doi.org/10.1172/JCI3428
  110. Petrache, I., Otterbein, L. E., Alam, J., Wiegand, G. W. and Choi, A. M. (2000) Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. Am. J. Physiol. Lung. Cell. Mol. Physiol. 278, 312-319. https://doi.org/10.1021/tx034154e
  111. Petzer, J. P., Navamal, M., Johnson, J. K., Kwak, M. K., Kensler, T. W. and Fishbein, J. C. (2003) Phase 2 enzyme induction by the major metabolite of oltipraz. Chem. Res. Toxicol. 16, 1463-1469. https://doi.org/10.1021/tx034154e
  112. Polte, T., Abate, A., Dennery, P. A. and Schroder, H. (2000) Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb. Vasc. Biol. 20, 1209-1215. https://doi.org/10.1006/jmcc.1997.0565
  113. Polte, T., Oberle, S. and Schroder, H. (1997) The nitric oxide donor SIN-1 protects endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity: possible role for cyclic GMP and heme oxygenase. J. Mol. Cell. Cardiol. 29, 3305-3310. https://doi.org/10.1006/jmcc.1997.0565
  114. Poss, K. D. and Tonegawa, S. (1997) Reduced stress defense in heme oxygenase 1-deficient cells. Proc. Natl. Acad. Sci. USA 94, 10925-10930. https://doi.org/10.1089/ars.2005.7.1688
  115. Prawan A., Kundu, J. K. and Surh A. J. (2005) Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection. Antioxid Redox Signal 7, 1688-1703. https://doi.org/10.1089/ars.2005.7.1688
  116. Primiano, T., Kensler, T. W., Kuppusamy, P., Zweier, J. L. and Sutter, T. R. (1996) Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones. Carcinogenesis 17, 2291-2296. https://doi.org/10.1093/carcin/17.11.2291
  117. Roebuck, B. D., Curphey, T. J., Li, Y., Baumgartner, K. J., Bodreddigari, S., Yan, J., Gange, SJ, Kensler, T.W. and Sutter, T.R. (2003) Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltipraz. Carcinogenesis 24, 1919-1928. https://doi.org/10.1093/carcin/bgg173
  118. Salinas, M., Diaz, R., Abraham, N. G., Ruiz de Galarreta, C. M. and Cuadrado, A. (2003) Nerve growth factor protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a phosphatidylinositol 3-kinase-dependent manner. J. Biol. Chem. 278, 13898-13904. https://doi.org/10.1074/jbc.M209164200
  119. Salinas, M., Wang, J., Rosa de Sagarra, M., Martin, D., Rojo, A. I, Martin-Perez, J., Ortiz de Montellano, P. R. and Cuadrado, A. (2004) Protein kinase Akt/PKB phosphorylates heme oxygenase-1 in vitro and in vivo. FEBS Lett 578, 90-94. https://doi.org/10.1016/j.febslet.2004.10.077
  120. Sarady, J. K., Zuckerbraun, B. S., Bilban, M., Wagner, O., Usheva, A., Liu, F., Ifedigbo, E., Zamora, R., Choi, A. M. and Otterbein, L.E. (2004) Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 18, 854-856. https://doi.org/10.1002/hep.20450
  121. Sass, G., Seyfried, S., Parreira Soares, M., Yamashita, K., Kaczmarek, E., Neuhuber, W. L. and Tiegs, G. (2004) Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury. Hepatology 40, 1128-1135. https://doi.org/10.1002/hep.20450
  122. Sass, G., Soares, M. C., Yamashita, K., Seyfried, S., Zimmermann, W. H., Eschenhagen, T., Kaczmarek, E., Ritter, T., Volk, H. D. and Tiegs, G. (2003) Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology 38, 909-918. https://doi.org/10.1038/sj.bjp.0706241
  123. Sawle, P., Foresti, R., Mann, B. E., Johnson, T. R., Green, C. J. and Motterlini, R. (2005) Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br. J. Pharmacol. 145, 800-810. https://doi.org/10.1038/sj.bjp.0706241
  124. Schiaffonati, L. and Tiberio L. (1997) Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress-inducible genes. Liver 17, 183-191. https://doi.org/10.1111/j.1600-0676.1997.tb00804.x
  125. Schmidt, R., Hoetzel, A., Baechle, T., Loop, T., Humar, M., Bauer, M., Pahl, H. L., Geiger, K. K. and Pannen, B. H. (2004) Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo. J. Hepatol. 41, 706-713. https://doi.org/10.1016/j.jhep.2004.07.004
  126. Seubert, J. M., Webb, C. D. and Bend, J. R. (2002) Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner. J. Biochem. Mol. Toxicol. 16, 96-106. https://doi.org/10.1002/jbt.10023
  127. Shan, Y., Lambrecht, R. W. and Bonkovsky, H. L. (2004) Identification of key elements that are responsible for hememediated induction of the avian heme oxygenase-1 gene. Biochim. Biophys. Acta 1679, 87-94. https://doi.org/10.1207/S15327914NC352_10
  128. Sheen, L. Y., Chen, H. W., Kung, Y. L, Liu, C. T. and Lii, C. K. (1999) Effects of garlic oil and its organosulfur compounds on the activities of hepatic drug-metabolizing and antioxidant enzymes in rats fed high- and low-fat diets. Nutr. Cancer 35, 160-166. https://doi.org/10.1207/S15327914NC352_10
  129. Stocker, R., Glazer, A. N. and Ames, B. N. (1987) Antioxidant activity of albumin-bound bilirubin. Proc. Natl. Acad. Sci. USA 84, 5918-5922. https://doi.org/10.1126/science.3029864
  130. Stocker, R., Yamamoto, Y., McDonagh, A. F., Glazer, A. N. and Ames, B. N. (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235, 1043-1046. https://doi.org/10.1126/science.3029864
  131. Suematsu, M., Goda, N., Sano, T., Kashiwagi, S., Egawa, T., Shinoda, Y. and Ishimura Y. (1995) Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J. Clin. Invest. 96, 2431-2437. https://doi.org/10.1172/JCI118300
  132. Takahashi, T., Morita, K., Akagi, R. and Sassa, S. (2004). Heme oxygenase-1: A novel therapeutic target in oxidative tissue injuries. Curr. Med. Chem. 11, 1545-1561. https://doi.org/10.2174/0929867043365080
  133. Tamion, F., Richard, V., Bonmarchand, G., Leroy, J., Lebreton, J. P. and Thuillez, C., (2001) Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock. Am. J. Respir. Crit. Care Med. 164, 1933-1938. https://doi.org/10.1038/sj.bjc.6600830
  134. Tanaka, S., Akaike, T., Fang, J., Beppu, T., Ogawa, M., Tamura, F., Miyamoto, Y. and Maeda, H. (2003) Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour. Br. J. Cancer. 88, 902-909. https://doi.org/10.1038/sj.bjc.6600830
  135. Trakshel, G. M., Kutty, R. K, and Maines, M. D. (1986) Purification and characterization of the major constitutive form of testicular heme oxygenase. The non inducible isoform. J. Biol. Chem. 261, 11131-11137. https://doi.org/10.1093/carcin/14.4.761
  136. Tyrrell, R. M., Applegate, L. A. and Tromvoukis, Y. (1993) The proximal promoter region of the human heme oxygenase gene contains elements involved in stimulation of transcriptional activity by a variety of agents including oxidants. Carcinogenesis 14, 761-765. https://doi.org/10.1093/carcin/14.4.761
  137. Wang, X. H., Wang, K., Zhang, F., Li, X. C., Li, J., De, W., Guo, J., Qian, X. F. and Fan, Y. (2005) Heme oxygenase-1 alleviates ischemia/reperfusion injury in aged liver. World J. Gastroenterol. 11, 690-694. https://doi.org/10.3748/wjg.v11.i5.690
  138. Wang, X. H., Wang, K., Zhang, F., Li, X. C., Qian, X. F., Cheng, F., Li, G. Q. and Fan Y. (2004) Alleviating ischemiareperfusion injury in aged rat liver by induction of heme oxygenase-1. Transplant Proc. 36, 2917-2923. https://doi.org/10.1016/j.transproceed.2004.10.066
  139. Wijayanti, N., Huber, S., Samoylenko, A., Kietzmann, T. and Immenschuh, S. (2004) Role of NF-kappaB and p38 MAP kinase signaling pathways in the lipopolysaccharide-dependent activation of heme oxygenase-1 gene expression. Antioxid. Redox Signal 6, 802-810. https://doi.org/10.2174/1568006033481410
  140. Wunder, C, and Porter, R. F. (2003) The heme oxygenase system: Its role in liver inflammation. Curr. Drug Target- Cardiovas. Haematological Disorders, 3, 199-208. https://doi.org/10.2174/1568006033481410
  141. Wunder, C., Brock, R. W., McCarter, S. D., Bihari, A., Harris, K., Eichelbronner, O and Potter, R. F. (2002) Inhibition of haem oxygenase activity increases leukocyte accumulation in the liver following limb ischaemia-reperfusion in mice. J. Physiol. 540, 1013-1021. https://doi.org/10.1113/jphysiol.2001.015446
  142. Yachie, A., Niida, Y., Wada, T., Igarashi, N., Kaneda, H., Toma, T., Ohta, K., Kasahara, Y. and Koizumi, S. (1999) Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest. 103, 129-135. https://doi.org/10.1172/JCI4165
  143. Yamasaki, A., Takahashi, T., Suzuki, T., Fujiwara, T., Hirakawa, M., Ohmori, E. and Akagi R. (2001) Differential effects of isoflurane and halothane on the induction of heat shock proteins. Biochem. Pharmacol. 62, 375-382. https://doi.org/10.1016/S0006-2952(01)00664-5
  144. Yang, C. S., Chhabra, S. K., Hong, J. Y. and Smith, T. J. (2001) Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J. Nutr. 131, 1041-1045. https://doi.org/10.1111/j.1432-1033.1988.tb13811.x
  145. Yoshida, T., Biro, P., Cohen, T., Muller, R. M. and Shibahara, S. (1988) Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur. J. Biochem. 171, 457-461. https://doi.org/10.1111/j.1432-1033.1988.tb13811.x
  146. Zhang, D. D. and Hannink, M. (2003) Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol. Cell. Biol. 23, 8137-8151. https://doi.org/10.1128/MCB.23.22.8137-8151.2003

Cited by

  1. The vampire in medical perspective: myth or malady? vol.107, pp.11, 2014, https://doi.org/10.1093/qjmed/hcu159
  2. Chitosan oligosaccharides reduce acetaminophen-induced hepatotoxicity by suppressing CYP-mediated bioactivation vol.12, 2015, https://doi.org/10.1016/j.jff.2014.11.014
  3. Heme as a Magnificent Molecule with Multiple Missions: Heme Determines Its Own Fate and Governs Cellular Homeostasis vol.213, pp.1, 2007, https://doi.org/10.1620/tjem.213.1
  4. Rat Primary Hepatocytes Show Enhanced Performance and Sensitivity to Acetaminophen During Three-Dimensional Culture on a Polystyrene Scaffold Designed for Routine Use vol.9, pp.5, 2011, https://doi.org/10.1089/adt.2011.0371
  5. Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease vol.39, pp.8, 2015, https://doi.org/10.1038/ijo.2015.46
  6. Iron homeostasis and its regulators over the course of chronic hepatitis C vol.9, pp.9, 2014, https://doi.org/10.2217/fvl.14.63
  7. Hemopexin Prevents Endothelial Damage and Liver Congestion in a Mouse Model of Heme Overload vol.173, pp.1, 2008, https://doi.org/10.2353/ajpath.2008.071130
  8. Lipotoxicity and steatohepatitis in an overfed mouse model for non-alcoholic fatty liver disease vol.1812, pp.4, 2011, https://doi.org/10.1016/j.bbadis.2011.01.003
  9. Upregulation of heat shock protein 32 with hemin alleviates acute heat-induced hepatic injury in mice vol.19, pp.5, 2014, https://doi.org/10.1007/s12192-014-0495-6
  10. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes vol.447, pp.4, 2014, https://doi.org/10.1016/j.bbrc.2014.04.073
  11. Nadroparin Sodium Activates Nrf2/HO-1 Pathway in Acetic Acid-Induced Colitis in Rats vol.35, pp.3, 2012, https://doi.org/10.1007/s10753-012-9431-z
  12. Ethyl 3,4-dihydroxy benzoate, a unique preconditioning agent for alleviating hypoxia-mediated oxidative damage in L6 myoblasts cells vol.65, pp.1, 2015, https://doi.org/10.1007/s12576-014-0348-1
  13. The Nrf2/HO-1 Axis in Cancer Cell Growth and Chemoresistance vol.2016, 2016, https://doi.org/10.1155/2016/1958174
  14. Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction vol.128, pp.2, 2010, https://doi.org/10.1016/j.jep.2010.01.029
  15. Direct and indirect antioxidant properties of inducers of cytoprotective proteins 2008, https://doi.org/10.1002/mnfr.200700195
  16. Pleiotropic Effects of Proton Pump Inhibitors
    Guest Editor: Yuji Naito

    Immune and Inflammatory Responses in GERD and Lansoprazole vol.41, pp.2, 2007, https://doi.org/10.3164/jcbn.2007012
  17. Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury vol.6, pp.2, 2016, https://doi.org/10.7603/s40681-016-0009-1
  18. Hepatic ischemia-reperfusion injury and therapeutic strategies to alleviate cellular damage vol.41, pp.2, 2011, https://doi.org/10.1111/j.1872-034X.2010.00765.x
  19. Chlorella Ethanol Extract Induced Phase II Enzyme Through NFE2L2 (Nuclear Factor [Erythroid-Derived] 2-Like 2, NRF2) Activation and Protected Ethanol-Induced Hepatoxicity vol.18, pp.2, 2015, https://doi.org/10.1089/jmf.2014.3159
  20. Green tea protects human osteoblasts from cigarette smoke-induced injury: possible clinical implication vol.397, pp.3, 2012, https://doi.org/10.1007/s00423-011-0882-8
  21. Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages vol.431, pp.3, 2013, https://doi.org/10.1016/j.bbrc.2012.12.143
  22. Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide vol.34, pp.11, 2014, https://doi.org/10.1016/j.nutres.2014.10.003
  23. The role of aryl hydrocarbon receptor in regulation of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells vol.180, pp.2, 2009, https://doi.org/10.1016/j.cbi.2009.03.011
  24. Protective role of c-Jun N-terminal kinase 2 in acetaminophen-induced liver injury vol.374, pp.1, 2008, https://doi.org/10.1016/j.bbrc.2008.06.065
  25. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway vol.273, pp.1, 2013, https://doi.org/10.1016/j.taap.2013.08.019
  26. Correlation between heat shock protein 32 and chronic heat-induced liver injury in developing mice vol.38, pp.8, 2013, https://doi.org/10.1016/j.jtherbio.2013.08.006
  27. The α-methylene-γ-butyrolactone moiety in dehydrocostus lactone is responsible for cytoprotective heme oxygenase-1 expression through activation of the nuclear factor E2-related factor 2 in HepG2 cells vol.565, pp.1-3, 2007, https://doi.org/10.1016/j.ejphar.2007.02.053
  28. Nrf2 activation in the liver of rats subjected to a preconditioning sub-chronic iron protocol vol.5, pp.2, 2014, https://doi.org/10.1039/C3FO60265F
  29. Repair and regeneration of the human endometrium vol.4, pp.3, 2009, https://doi.org/10.1586/eog.09.6
  30. Salvianolic Acid B Reducing Portal Hypertension Depends on Macrophages in Isolated Portal Perfused Rat Livers with Chronic Hepatitis vol.2012, 2012, https://doi.org/10.1155/2012/786365
  31. Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells vol.654, pp.3, 2011, https://doi.org/10.1016/j.ejphar.2010.12.027
  32. Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish vol.232, pp.9, 2007, https://doi.org/10.3181/0703-RM-77
  33. Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction vol.84, pp.7, 2012, https://doi.org/10.1016/j.bcp.2012.07.019
  34. Proton pump inhibitors as also inhibitors of atrial fibrillation vol.718, pp.1-3, 2013, https://doi.org/10.1016/j.ejphar.2013.07.043
  35. In vivo delivery of transcription factors with multifunctional oligonucleotides vol.14, pp.7, 2015, https://doi.org/10.1038/nmat4269
  36. Hepatitis C virus core protein compromises iron-induced activation of antioxidants in mice and HepG2 cells vol.82, pp.5, 2010, https://doi.org/10.1002/jmv.21661
  37. Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release vol.35, pp.4, 2013, https://doi.org/10.1007/s10059-013-0021-1
  38. Functional Expression of Heme Oxygenase-1 in Human Differentiated Epidermis and Its Regulation by Cytokines vol.129, pp.11, 2009, https://doi.org/10.1038/jid.2009.119
  39. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation vol.2015, 2015, https://doi.org/10.1155/2015/854359
  40. Intermittent hypoxia upregulates hepatic heme oxygenase-1 and ferritin-1, thereby limiting hepatic pathogenesis in rats fed a high-fat diet vol.50, pp.7, 2016, https://doi.org/10.3109/10715762.2016.1170125
  41. Imaging Endogenous Bilirubins with Two-Photon Fluorescence of Bilirubin Dimers vol.87, pp.15, 2015, https://doi.org/10.1021/acs.analchem.5b01903
  42. Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages vol.58, 2013, https://doi.org/10.1016/j.fct.2013.04.002
  43. Hepatoprotective effect ofCommiphora myrrhaagainstd-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes vol.53, pp.12, 2015, https://doi.org/10.3109/13880209.2015.1005754
  44. Upregulation of HO-1 with Haemin Alleviates LPS-Stimulated Pro-inflammatory Responses Through Downregulation of p38 Signalling Pathways in Rat Liver vol.82, pp.5, 2015, https://doi.org/10.1111/sji.12352
  45. Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation vol.55, 2013, https://doi.org/10.1016/j.fct.2012.12.043
  46. Antineuroinflammatory effects of lycopene via activation of adenosine monophosphate-activated protein kinase-α1/heme oxygenase-1 pathways vol.35, pp.1, 2014, https://doi.org/10.1016/j.neurobiolaging.2013.06.020
  47. Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation vol.136, pp.1, 2011, https://doi.org/10.1016/j.jep.2011.04.030
  48. Short Passive Cooling Protects Rats During Hepatectomy by Inducing Heat Shock Proteins and Limiting the Induction of Pro-Inflammatory Cytokines vol.158, pp.1, 2010, https://doi.org/10.1016/j.jss.2008.08.030
  49. Altered Vascular Function, Arterial Stiffness, and Antioxidant Gene Responses in Pediatric Thalassemia Patients vol.33, pp.7, 2012, https://doi.org/10.1007/s00246-012-0225-8
  50. The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1 vol.21, pp.5, 2016, https://doi.org/10.3390/molecules21050594
  51. Pathomechanisms of Ischemia-Reperfusion Injury as the Basis for Novel Preventive Strategies: Is It Time for the Introduction of Pleiotropic Compounds? vol.39, pp.2, 2007, https://doi.org/10.1016/j.transproceed.2007.01.022
  52. A Phosphodiesterase III Inhibitor Protects Rat Liver From Sinusoidal Obstruction Syndrome Through Heme Oxygenase-1 Induction vol.249, pp.5, 2009, https://doi.org/10.1097/SLA.0b013e3181a38ed5
  53. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice vol.51, 2013, https://doi.org/10.1016/j.fct.2012.10.021
  54. Luteolin and luteolin-7-O-glucoside strengthen antioxidative potential through the modulation of Nrf2/MAPK mediated HO-1 signaling cascade in RAW 264.7 cells vol.65, 2014, https://doi.org/10.1016/j.fct.2013.12.017
  55. Heme Oxygenase-1: Its Therapeutic Roles in Inflammatory Diseases vol.9, pp.1, 2009, https://doi.org/10.4110/in.2009.9.1.12
  56. CO metabolism, sensing, and signaling vol.38, pp.1, 2012, https://doi.org/10.1002/biof.192
  57. Up-regulation of hepatic heme oxygenase-1 expression by locally induced interleukin-6 in rats administered carbon tetrachloride intraperitoneally vol.179, pp.3, 2008, https://doi.org/10.1016/j.toxlet.2008.04.012
  58. Oxidative stress and regulation of anti-oxidant enzymes in cytochrome P4502E1 transgenic mouse model of non-alcoholic fatty liver vol.25, pp.6, 2010, https://doi.org/10.1111/j.1440-1746.2009.06196.x
  59. Echinacea Alkamides Prevent Lipopolysaccharide/d-Galactosamine- Induced Acute Hepatic Injury through JNK Pathway-Mediated HO-1 Expression vol.59, pp.22, 2011, https://doi.org/10.1021/jf202958r
  60. Enterovirus 71 induces integrin β1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: Role of HO-1/CO in viral replication vol.226, pp.12, 2011, https://doi.org/10.1002/jcp.22677
  61. Heme Enzyme Structure and Function vol.114, pp.7, 2014, https://doi.org/10.1021/cr400415k
  62. Guasha-induced hepatoprotection in chronic active hepatitis B: A case study vol.412, pp.17-18, 2011, https://doi.org/10.1016/j.cca.2011.05.009
  63. HO-1 up-regulation: A key point in high-risk neuroblastoma resistance to bortezomib vol.1842, pp.4, 2014, https://doi.org/10.1016/j.bbadis.2013.12.008
  64. Xanthohumol induces phase II enzymes via Nrf2 in human hepatocytes in vitro vol.27, pp.1, 2013, https://doi.org/10.1016/j.tiv.2012.10.008
  65. Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1 vol.9, pp.12, 2009, https://doi.org/10.1016/j.intimp.2009.08.015
  66. Inhibition of the NADPH oxidase regulates heme oxygenase 1 expression in chronic myeloid leukemia vol.118, pp.13, 2012, https://doi.org/10.1002/cncr.26621
  67. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress vol.1830, pp.10, 2013, https://doi.org/10.1016/j.bbagen.2013.06.028
  68. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells vol.171, pp.1, 2014, https://doi.org/10.1111/bph.12440
  69. Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease vol.12, pp.4, 2012, https://doi.org/10.5812/hepatmon.5956
  70. Carbon monoxide blocks oxidative stress-induced hepatocyte apoptosis via inhibition of the p54 JNK isoform vol.44, pp.7, 2008, https://doi.org/10.1016/j.freeradbiomed.2007.12.011
  71. Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme vol.75, pp.11, 2008, https://doi.org/10.1016/j.bcp.2008.02.029
  72. The many faces of nitric oxide: cytotoxic, cytoprotective or both vol.19, pp.7, 2007, https://doi.org/10.1111/j.1365-2982.2007.00958.x
  73. Association of lower total bilirubin level with statin usage: The United States National Health and Nutrition Examination Survey 1999–2008 vol.219, pp.2, 2011, https://doi.org/10.1016/j.atherosclerosis.2011.07.094
  74. Effects of Paeonol on Anti-Neuroinflammatory Responses in Microglial Cells vol.16, pp.4, 2015, https://doi.org/10.3390/ijms16048844
  75. Hepatoprotective and Antioxidative Activities ofCornus officinalisagainst Acetaminophen-Induced Hepatotoxicity in Mice vol.2012, 2012, https://doi.org/10.1155/2012/804924
  76. Morin Induces Heme Oxygenase-1 via ERK-Nrf2 Signaling Pathway vol.18, pp.3, 2013, https://doi.org/10.15430/JCP.2013.18.3.249
  77. Effect of curcumin on hepatic heme oxygenase 1 expression in high fat diet fed rats: is there a triangular relationship? vol.92, pp.10, 2014, https://doi.org/10.1139/cjpp-2014-0174
  78. TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells vol.66, 2014, https://doi.org/10.1016/j.fct.2014.01.019
  79. α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats vol.32, pp.10, 2012, https://doi.org/10.1111/j.1478-3231.2012.02857.x
  80. Differential expression of HO-1 and CYP1A2 during up-regulation of ERK in stressed fish hepatocytes vol.187, pp.1, 2015, https://doi.org/10.1007/s10661-014-4147-1
  81. Sake lees hydrolysate protects against acetaminophen-induced hepatotoxicity via activation of the Nrf2 antioxidant pathway 2017, https://doi.org/10.3164/jcbn.17-21
  82. Steroid regulation of menstrual bleeding and endometrial repair vol.13, pp.4, 2012, https://doi.org/10.1007/s11154-012-9228-2
  83. Chemical-induced coordinated and reciprocal changes in heme metabolism, cytochrome P450 synthesis and others in the liver of humans and rodents vol.41, pp.Special, 2016, https://doi.org/10.2131/jts.41.SP89
  84. Subtle interplay of endogenous bioactive gases (NO, CO and H2S) in inflammation vol.32, pp.8, 2009, https://doi.org/10.1007/s12272-009-1806-9
  85. Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats vol.35, pp.4, 2012, https://doi.org/10.1007/s10753-012-9470-5
  86. The organophosphate chlorpyrifos disturbs redox balance and triggers antioxidant defense mechanisms in JEG-3 cells vol.34, pp.9, 2013, https://doi.org/10.1016/j.placenta.2013.06.007
  87. Epigallocatechin Gallate Attenuates Proliferation and Oxidative Stress in Human Vascular Smooth Muscle Cells Induced by Interleukin-1βvia Heme Oxygenase-1 vol.2014, 2014, https://doi.org/10.1155/2014/523684
  88. Effects of treatment with hydrogen sulfide on methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats vol.29, pp.1, 2014, https://doi.org/10.1111/jgh.12389
  89. Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression vol.38, pp.2, 2014, https://doi.org/10.1016/j.etap.2014.08.004
  90. α-pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells vol.19, pp.5, 2010, https://doi.org/10.1007/s10068-010-0189-5
  91. Heme oxygenase-1 could mediate the protective effects of hyperbaric oxygen preconditioning against hepatic ischemia-reperfusion injury in rats vol.38, pp.10, 2011, https://doi.org/10.1111/j.1440-1681.2011.05560.x
  92. Anti-angiogenic properties of coenzyme Q0 through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling in TNF-α-activated human endothelial cells vol.98, pp.1, 2015, https://doi.org/10.1016/j.bcp.2015.09.003
  93. Nrf2 protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis vol.256, pp.2, 2011, https://doi.org/10.1016/j.taap.2011.07.019
  94. Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview vol.6, 2016, https://doi.org/10.3389/fphys.2015.00363
  95. Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress vol.21, pp.1, 2016, https://doi.org/10.15430/JCP.2016.21.1.41
  96. Lipid hydroperoxides from processed dietary oils enhance growth of hepatocarcinoma cells vol.52, pp.3, 2008, https://doi.org/10.1002/mnfr.200700149
  97. Bilirubin participates in protecting of heme oxygenase-1 induction by quercetin against ethanol hepatotoxicity in cultured rat hepatocytes vol.47, pp.2, 2013, https://doi.org/10.1016/j.alcohol.2012.10.006
  98. Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury vol.48, pp.5, 2008, https://doi.org/10.1002/hep.22491
  99. Hawthorn (Crataegus oxyacanthaL.) Bark Extract Regulates Antioxidant Response Element (ARE)-Mediated Enzyme ExpressionViaNrf2 Pathway Activation in Normal Hepatocyte Cell Line vol.28, pp.4, 2014, https://doi.org/10.1002/ptr.5035
  100. Antrodia salmonea inhibits TNF-α-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-κB and up-regulation of Nrf2 signaling pathways vol.151, pp.1, 2014, https://doi.org/10.1016/j.jep.2013.10.052
  101. Neuronal Apoptosis in Neurodegeneration vol.9, pp.8, 2007, https://doi.org/10.1089/ars.2007.1511
  102. The protective role of HO-1 and its generated products (CO, bilirubin, and Fe) in ethanol-induced human hepatocyte damage vol.296, pp.6, 2009, https://doi.org/10.1152/ajpgi.00555.2007