Journal of Gastroenterology

, 42:96

Molecular mechanism of iron metabolism and overload in chronic hepatitis C

  • Masahiko Kaito


  1. 1.
    Hentze, MW, Muckenthaler, MU, Andrews, NC 2004Balancing acts: molecular control of mammalian iron metabolismCell11728597CrossRefPubMedGoogle Scholar
  2. 2.
    Fenton, HJH 1894Oxidation of tartaric acid in presence of ironJ Chem Soc65899910Google Scholar
  3. 3.
    McKie, AT, Barrow, D, Latunde, GO, Rolfs, A, Sager, G, Mudaly, E,  et al. 2001An iron-regulated ferric reductase associated with the absorption of dietary ironScience29117559CrossRefPubMedGoogle Scholar
  4. 4.
    Gunshin, H, Mackenzie, B, Gunshin, Y, Romero, MF, Boron, WF, Nussberger, S,  et al. 1997Cloning and characterization of a mammalian proton-coupled metal-ion transporterNature3884828CrossRefPubMedGoogle Scholar
  5. 5.
    Donovan, A, Brownlie, A, Zhou, Y, Shepard, J, Pratt, SJ, Moynihan, J,  et al. 2000Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporterNature40377681CrossRefPubMedGoogle Scholar
  6. 6.
    Vulpe, CD, Kuo, YM, Murphy, T, Cowley, L, Askwith, C, Libina, N,  et al. 1999Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the ala mouseNat Genet211959CrossRefPubMedGoogle Scholar
  7. 7.
    von Bockxmeer, FM, Morgan, EH 1977Identification of transferring receptors in reticulocytesBiochim Biophys Acta46843750CrossRefGoogle Scholar
  8. 8.
    Trinder, D, Zak, O, Aisen, P 1996Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expressionHepatology23151220CrossRefPubMedGoogle Scholar
  9. 9.
    Kawabata, H, Yang, R, Hirama, T, Vuong, PT, Kawano, S, Gombart, AF,  et al. 1999Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like familyJ Biol Chem2742082632CrossRefPubMedGoogle Scholar
  10. 10.
    Park, CH, Volore, EV, Waring, AJ, Ganz, T 2001Hepcidin, a urinary antimicrobial peptide synthesized in the liverJ Biol Chem276780610CrossRefPubMedGoogle Scholar
  11. 11.
    Nicoras, G, Viatte, L, Bennoun, M, Beaumont, C, Kahn, A, Vaulont, S 2002Hepcidin, a new iron regulatory peptideBlood Cells Mol Dis2932735CrossRefGoogle Scholar
  12. 12.
    Ganz, T 2003Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammationBlood1027838CrossRefPubMedGoogle Scholar
  13. 13.
    Nemeth, E, Tuttle, MS, Powelson, J, Vaughn, MB, Donovan, A, Ward, DM,  et al. 2004Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalizationScience30620903CrossRefPubMedGoogle Scholar
  14. 14.
    Di Bisceglie, AM, Axiotis, CA, Hoofnagle, JH, Bacon, BR 1992Measurements of iron status in patients with chronic hepatitisGastroenterology102210813PubMedGoogle Scholar
  15. 15.
    Farinati, F, Cardin, R, De Maria, N, Della Libera, G, Marafin, C, Lecis, E,  et al. 1995Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitisJ Hepatol2244956CrossRefPubMedGoogle Scholar
  16. 16.
    Isomura, T, Yano, M, Hayashi, H, Sakamoto, N 1992Excess iron in the liver of patients with chronic hepatitis CJ Clin Electron Microsc252317Google Scholar
  17. 17.
    Bassett, SE, Di Bisceglie, AM, Bacon, BR, Sharp, RM, Govindarajan, S, Hubbard, GB,  et al. 1999Effects of iron loading on pathogenicity in hepatitis C virus-infected chimpanzeesHepatology29188492CrossRefPubMedGoogle Scholar
  18. 18.
    Hayashi, H, Takikawa, T, Nishimura, N, Yano, M, Isomura, T, Sakamoto, N 1994Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis CAm J Gastroenterol899868PubMedGoogle Scholar
  19. 19.
    Hayashi, H, Takikawa, T, Nishimura, N, Yano, M 1995Serum aminotransferase levels as an indicator of the effectiveness of venesection for chronic hepatitis CJ Hepatol2226871CrossRefPubMedGoogle Scholar
  20. 20.
    Iwasa, M, Kaito, M, Ikoma, J, Kobayashi, Y, Tanaka, Y, Higuchi, K,  et al. 2002Dietary iron restriction improves aminotransferase levels in chronic hepatitis C patientsHepatogastroenterology4952931PubMedGoogle Scholar
  21. 21.
    Iwasa, M, Iwata, K, Kaito, M, Ikoma, J, Yamamoto, M, Takeo, M,  et al. 2004Efficacy of long-term dietary restriction of total calories, fat, iron, and protein in patients with chronic hepatitis C virusNutrition2036871CrossRefPubMedGoogle Scholar
  22. 22.
    Takeo, M, Kobayashi, Y, Fujita, N, Urawa, N, Iwasa, M, Horiike, S,  et al. 2005Upregulation of transferrin receptor 2 and ferroportin 1 mRNA in the liver of patients with chronic hepatitis CJ Gastroenterol Hepatol205629CrossRefPubMedGoogle Scholar
  23. 23.
    Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R, Tanaka H, et al. Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C. Mol Med 2007;13Google Scholar
  24. 24.
    Kato, J, Kobune, M, Nakamura, T, Kuroiwa, G, Takada, K, Takimoto, R,  et al. 2001Normalization of elevated hepatic 8-hydroxy-2′-deoxyguanousine levels in chronic hepatitis C patients by phlebotomy and low iron dietCancer Res618697702PubMedGoogle Scholar
  25. 25.
    Paradis, V, Mathurin, P, Kollinger, M, Imbert-Bismut, F, Charlotte, F, Piton, A,  et al. 1997In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological featuresJ Clin Pathol504016CrossRefPubMedGoogle Scholar
  26. 26.
    Coussens, LM, Werb, Z 2002Inflammation and cancerNature4208607CrossRefPubMedGoogle Scholar
  27. 27.
    Horiike, S, Kawanishi, S, Kaito, M, Ma, N, Tanaka, H, Fujita, N,  et al. 2005Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis CJ Hepatol4340310CrossRefPubMedGoogle Scholar
  28. 28.
    Loeb, LA, Preston, BD 1986Mutagenesis by apurinic/apyrimidinic sitesAnnu Rev Genet2020130CrossRefPubMedGoogle Scholar
  29. 29.
    Yermilov, V, Rubio, J, Ohshima, H 1995Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurinationFEBS Lett37620710CrossRefPubMedGoogle Scholar
  30. 30.
    Huang, H, Fuji, H, Sankila, A, Mahler-Araujo, BM, Matsuda, M, Cathomas, G,  et al. 1999Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infectionAm J Pathol1551795801PubMedGoogle Scholar
  31. 31.
    Furutani, T, Hino, K, Okuda, M, Gondo, T, Nishina, S, Kitase, A,  et al. 2006Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyproteinGastroenterology130208798CrossRefPubMedGoogle Scholar
  32. 32.
    Yano, M, Hayashi, H, Yoshioka, K, Saito, Y, Niitsu, Y, Kato, J,  et al. 2004A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in JapanJ Gastroenterol395704CrossRefPubMedGoogle Scholar
  33. 33.
    Kaito, M, Iwasa, M, Kobayashi, Y, Fujita, N, Tanaka, H, Gabazza, EC,  et al. 2006Decreased lipid peroxidation after phlebotomy in patients with chronic hepatitis CJ Gastroenterol419212CrossRefPubMedGoogle Scholar
  34. 34.
    Tanaka, N, Horiuchi, A, Yamaura, T, Komatsu, M, Tanaka, E, Kiyosawa, K 2007Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot studyJ Gastroenterol424955CrossRefPubMedGoogle Scholar
  35. 35.
    Sangiovanni, A, Colombo, E, Radaelli, F, Bortoli, A, Bovo, G, Casiraghi, MA,  et al. 2001Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhotic patientsAm J Gastroenterol96157580CrossRefPubMedGoogle Scholar
  36. 36.
    Iwata, K, Iwasa, M, Hara, N, Matsumoto, A, Kobayashi, Y, Watanabe, S,  et al. 2006Iron content and consumption of health foods by patients with chronic hepatitis CJ Gastroenterol4191920CrossRefPubMedGoogle Scholar
  37. 37.
    Patek, AJ, Post, J 1941Treatment of cirrhosis of the liver by a nutritious diet and supplements rich in vitamin B complexJ Clin Invest2048190CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Masahiko Kaito
    • 1
  1. 1.Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical ScienceInstitute of Medical Science, Mie University Graduate School of MedicineMieJapan

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